Gene expression profiles associated with chronic allograft nephropathy

ABSTRACT

By a genome-wide gene analysis of expression profiles of over 50,000 known or putative gene sequences in peripheral blood, the present inventors have identified a consensus set of gene expression-based molecular biomarkers associated with chronic allograft nephropathy and/or interstitial fibrosis and tubular atrophy CAN/IFTA and subtypes thereof. These genes sets are useful for diagnosis, prognosis, monitoring and/or subtyping of CAN/IFTA.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a nonprovisional and claims the benefit ofU.S. Ser. No. 61/224,328 and 61/224,317 each filed Jul. 9, 2009, andincorporated by reference in its entirety for all purposes.

STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSOREDRESEARCH OR DEVELOPMENT

This invention was made with government support under grant numbersAI063603 and AI084146 awarded by the National Institutes of Health. TheUS Government has certain rights in the invention.

BACKGROUND OF THE INVENTION

Kidney transplantation offers a significant improvement in lifeexpectancy and quality of life for patients with end stage renaldisease[1]. Unfortunately, a chronic, progressive allograft dysfunctionof uncertain etiology continues to be a primary cause of graftloss[2,3]. There has been some evolution of terminology for describingthe histological basis of this chronic, progressive nephropathy, whichis still commonly referred to as chronic allograft nephropathy (CAN) andmore recently as interstitial fibrosis and tubular atrophy (IFTA)[4-6].In current practice CAN refers to a clinical entity of a chronicprogressive loss of kidney transplant function associated with a risingserum creatinine and a falling creatinine clearance. In currentpractice, IFTA refers to the histological findings based on review of akidney transplant biopsy. Immunologic factors linked to CAN/IFTA areacute, sub-clinical and CAN/IFTA, HLA mismatching and circulatingdonor-specific anti-HLA antibodies[7,8]. Non-immunologic factors includehypertension, chronic toxicity of calcineurin inhibitors,hyperfiltration and diabetes mellitus[9-12]. The unifying mechanism isthought to be a progressive cycle of vascular and tissue injury,incomplete repair, compensatory hypertrophy, progressive interstitialfibrosis and nephron loss[13]. Moreover, increasing evidence issuggesting that the primary mechanism of CAN/IFTA is a chronicimmunological injury mediated by a combination of T cell andantibody-mediated immunity, in other words, chronic rejection.

As early as two years post kidney transplant, protocol biopsies haveshown that more than 50% of recipients have mild CAN/IFTA[2,15,16] andby 10 years over 50% of kidney transplant recipients have severeCAN/IFTA that is associated with diminishing graft function[2].Traditional kidney function measurements like serum creatinine andglomerular filtration rates used to predict CAN/IFTA have poorpredictive values[17] and a diagnosis requires a transplantbiopsy[18,19]. Predicting graft outcomes strictly based on the kidneybiopsy is difficult and this invasive procedure has significant costsand risks for patients. Thus, there is a pressing medical need toidentify minimally invasive biomarkers that are able to identify earlystages of CAN/IFTA at a time that changes in therapy may alter outcomes.

Rapidly evolving technologies for genomics have created newopportunities to develop minimally invasive biomarkers. Recent studies,including our own, have reported genes that are differentially expressedat the mRNA level in kidney biopsies in the presence ofCAN/IFTA[16,20,21]. The limitation of these studies is that they requirean invasive transplant biopsy. Others have reported analyzing urine andperipheral blood using RT-qPCR or proteomics to identify small numbersof potential biomarkers for CAN/IFTA, though none is validated forclinical use[22,23].

BRIEF SUMMARY OF THE INVENTION

The invention provides methods of prognosing, diagnosing or monitoringchronic allograft nephropathy and/or interstitial fibrosis and tubularatrophy (CAN/IFTA). The methods entail (a) determining expression levelsin a subject of at least 5 genes selected from the genes in Table A, B,C, D, E, F, G, H, I and/or J; and (b) prognosing diagnosing ormonitoring CAN/IFTA in a subject from the expression levels. Optionally,for each of the at least five genes, step (b) comprises comparing theexpression level of the gene in the subject to one or more referenceexpression levels of the gene associated with CAN/IFTA or lack ofCAN/IFTA. Optionally, step (b) further comprises for each of the atleast five genes assigning the expression level of the gene in thesubject a value or other designation providing an indication whether thesubject has or is at risk of CAN/IFTA. Optionally, the expression levelof each of the at least five genes is assigned a value on a normalizedscale of values associated with a range of expression levels in kidneytransplant patients with and without CAN/IFTA. Optionally, theexpression level of each of the at least five genes is assigned a valueor other designation providing an indication that the subject has is atrisk of CAN/IFTA, lacks and is not at risk of CAN/IFTA, or that theexpression level is uninformative. Optionally, step (b) furthercomprises, combining the values or designations for each of the genes toprovide a combined value or designation providing an indication whetherthe subject has or is at risk of CAN/IFTA. Optionally, the method isrepeated at different times on the subject.

In some methods, the subject is receiving a drug, and a change in thecombined value or designation over time provides an indication of theeffectiveness of the drug. Optionally, the subject has undergone akidney transplant within 1-10 years of performing step (a). Optionally,step (a) is performed on a blood sample of the subject. Optionally, theblood sample is a plasma sample. Optionally, step (a) is performed on atleast ten, 20, 40, or 100 genes from Table A, B, C, D, E, F, G, H, Iand/or J.

Some methods further comprise changing the treatment regime of thepatient responsive to the prognosing, diagnosing or monitoring step. Insome methods, the subject has received a drug before performing themethods, and the change comprises administering an additional drug oradministering a higher dose of the same drug. Some methods, furthercomprise performing an additional procedure, such as a kidney biopsy, todetect CAN/IFTA or risk thereof if the determining step provides anindication the subject has or is at risk of CAN/IFTA.

In some methods, the at least five genes are from Table A, B, C and/or Dexpression levels are determined at the mRNA level. In some methods, theat least five genes are from Tables E, F, G, H, I, and/or J andexpression levels are determined at the protein level. In some methods,step (b) is performed by a computer. In some methods, the at least fivegenes are selected from Tables C and D. In some methods, the at leastfive genes are selected from Table C. In some methods, the at least fivegenes are selected from Table D. In some methods, the at least fivegenes are selected from Table E and F or H and I and expression levelsare determined at the protein level.

The invention further provides an array, comprising a support orsupports bearing a plurality of nucleic acid probes complementary to aplurality of mRNAs fewer than 5000 in number, wherein the plurality ofmRNAs includes mRNAs expressed by at least five genes selected fromTables A, B, C, D. Optionally, the plurality of mRNAs are fewer than1000, or 100 in number. Optionally a plurality of nucleic acid probesare attached to a planar support or to beads. Optionally, the at leastfive genes are selected from Table C and D. Optionally, the at leastfive genes are selected from Table C. Optionally, the at least fivegenes are selected from Table D.

The invention further provides an array, comprising a support orsupports bearing a plurality of ligands that specifically bind to aplurality of proteins fewer than 5000 in number, wherein the pluralityof proteins includes at least five proteins selected from Tables E, F,G, H, I and/or J. Optionally, the plurality of proteins are fewer than1000 or 100 in number. Optionally, the plurality of ligands are attachedto a planar support or to beads. Optionally, the at least five proteinsare selected from Tables E and F and/or I and J. Optionally, the ligandsare different antibodies, wherein the different antibodies bind todifferent proteins of the plurality of proteins.

The invention further provides a method of expression analysis,comprising determining expression levels of up to 5000 genes in a samplefrom a subject having a kidney transplant, wherein the genes include atleast 5 genes selected from Table A, B, C, D, E, F, G, H, I and/or J.Optionally, the expression levels of up to 1000 or 100 genes aredetermined. The expression levels can be determined at the mRNA orprotein level. The levels can be determined by, for example,quantitative PCR or hybridization to an array.

The invention further provides methods of screening a compound foractivity in inhibiting or treating CAN/IFTA. The methods entail (a)administering the compound to a subject having or at risk of CAN/IFTA;(b) determining expression levels of at least five genes in the subjectselected from Table A, B, C, D, E, F, G, H, I, and/or J and speciesvariants thereof before and after administering the drug to the subject,and (c) determining whether the compound has activity in inhibiting ortreating CAN/IFTA from a change in expression levels of the genes afteradministering the compound. Optionally, step (c) comprises for each ofthe at least five changes assigning a value or designation depending onwhether the change in the expression level of the gene relative to oneor more reference levels indicating presence or absence of CAN/IFTA.Optionally, the method further comprises determining a combined value ordesignation for the at least five genes from the values or designationsdetermined for each gene. Optionally, the subject is human or a nonhumananimal model of CAN/IFTA.

The invention further provides methods of subtyping CAN/IFTA. Themethods entail (a) determining expression levels in a subject of atleast 5 genes selected from the genes in Tables A, B, C, D; E, F, G, H,I and/or J; and (b) determining a subtype of CAN/IFTA from theexpression levels. The subtype can be selected from the group consistingof stage 0, 1, 2, or 3 of CAN/IFTA. Optionally, the subtype is stage 0,stage 1 or stage 2 and/or 3. In some methods for each of the at leastfive genes, step (b) comprises comparing the expression level of thegene in the subject to one or more reference expression levels of thegene associated with the subtype of CAN/IFTA or lack of CAN/IFTA. Somemethods further comprise for each of the at least five genes assigningthe expression level of the gene in the subject a value or otherdesignation providing an indication whether the subject has or is atrisk of the subtype of CAN/IFTA. In some methods, the expression levelof each of the at least five genes is assigned a value on a normalizedscale of values associated with a range of expression levels in kidneytransplant patients with the subtype and without CAN/IFTA. In somemethods, the expression level of each of the at least five genes isassigned a value or other designation providing an indication that thesubject has or is at risk of the subtype of CAN/IFTA, lacks and is notat risk of the subtype of CAN/IFTA, or that the expression level isuninformative. In some methods, step (b) further comprises, combiningthe values or designations for each of the genes to provide a combinedvalue or designation providing an indication whether the subject has oris at risk of the subtype of CAN/IFTA. Some methods are repeated atdifferent times on the subject. In some methods, the subject isreceiving a drug, and a change in the combined value or designation overtime provides an indication of the effectiveness of the drug. In somemethods, the subject has undergone a kidney transplant within 1-10 yearsof performing step (a). Some methods are performed on a blood sample ofthe subject, such as a plasma or whole blood sample. Some methods areperformed on at least ten, 20, 40 or 100 genes selected from Tables A,B, C, D, E, F, G, H, I and/or J. Some methods further comprise changingthe treatment regime of the patient responsive to the whether thesubtype is present. In some methods, the subject has received a drugbefore performing the methods, and the change comprises administering anadditional drug or administering a higher dose of the same drug. Somemethods further comprise performing an additional procedure, such as akidney biopsy, to detect CAN/IFTA or risk thereof if the determiningstep provides an indication the subject has or is at risk of the subtypeof CAN/IFTA. Expression levels can be determined at the mRNA or proteinlevel. In some methods, step (b) is performed by a computer. In somemethods, the at least five genes are selected from Table C. In somemethods, the at least five genes are selected from Table D. In somemethods, the at least five genes are selected from Table E andexpression levels are determined at the protein level. In some methods,the at least five genes are selected from Table F and the expressionlevels are determined at the protein level. In some methods, the atleast five genes are selected from Table H and the expression levels aredetermined at the protein level. In some methods, the at least fivegenes are selected from Table I and the expression levels are determinedat the protein level.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1: Class prediction analysis of Banff 0 vs. Banff 1 (mild CAN/IFTA)based on Diagonal Linear Discriminant Analysis for the top 50 Banff 0vs. Banff 1 consensus genes ranked by p values. A) depicts the ReceiverOperating Characteristic (ROC) curves and provides the Sensitivity,Specificity, Positive Predictive Value (PPV) and Negative PredictiveValue (NPV);

FIG. 2: Class prediction analysis of Banff 0 vs. Banff 2,3 (moderate tosevere CAN/IFTA) based on Diagonal Linear Discriminant Analysis for thetop 50 Banff 0 vs. Banff 2,3 consensus genes ranked by p values. A)depicts the Receiver Operating Characteristic (ROC) curves and providesthe Sensitivity, Specificity, Positive Predictive Value (PPV) andNegative Predictive Value (NPV); B) depicts the heat map classifyingBanff 0 vs. Banff 2,3 using the top 50 consensus genes where (red) isup-regulated and (green) is down-regulated.

DEFINITIONS

The term Chronic Allograft Nephropathy/Interstitial Fibrosis and TubularAtrophy (CAN/IFTA) refers to a progressive, chronic, kidney tissueinjury that eventually causes a progressive, chronic deterioration ofkidney transplant function. The histological changes of CAN/IFTA can befound in protocol kidney transplant biopsies as early as 6 months posttransplant and frequently the clinical changes of progressive kidneytransplant dysfunction evolve subsequently over the next year or severalyears (e.g., six months to ten years). CAN/IFTA is usually a consequenceof combined immunological injury (e.g. chronic rejection) andnon-immunological damage (e.g. hypertensive nephrosclerosis, ornephrotoxicity of immunosuppressants like cyclosporine A), taking placemonths or years after transplantation and ultimately leading tohistologically detectable fibrosis and sclerosis of the transplant andprogressive loss of kidney function. Chronic rejection of a transplantedkidney is increasingly thought to be the major mechanism of CAN/IFTAmediated through both T cell mediated immunity and antibodies directedat antigens expressed in the kidney transplant. The hybrid term,CAN/IFTA includes histological changes and/or functional deteriorationof the kidneys or both. In some patients, the present methods canprovide an indication of histological changes before detectablefunctional deterioration of the kidneys has occurred, thereby allowingearly therapeutic intervention.

Transplantation is the transfer of tissues, cells or an organ from adonor into a recipient. If the donor and recipient as the same person,the graft is referred to as an autograft and as is usually the casebetween different individuals of the same species an allograft. Transferof tissue between species is referred to as a xenograft.

A biopsy is a specimen obtained from a living patient for diagnosticevaluation. Kidney biopsies can be obtained with a needle.

An average value can refer to any of a mean, median or mode.

A gene expression level is associated with a particular phenotype e.g.,presence of CAN/IFTA or a subtype thereof if the gene is differentiallyexpressed in a patient having the phenotype relative to a patientlacking the phenotype to a statistically significant extent. Unlessotherwise apparent from the context a gene expression level can bemeasured at the mRNA and/or protein level.

A target nucleic acids is a nucleic acid (often derived from abiological sample), to which a polynucleotide probe is designed tospecifically hybridize. The probe can detect presence, absence and/oramount of the target. The term can refer to the specific subsequence ofa larger nucleic acid to which the probe is directed or to the overallsequence (e.g., c DNA or mRNA) whose expression level it is desired todetect.

The term subject or patient can include human or non-human animals.Thus, the methods and described herein are applicable to both human andveterinary disease and animal models. Preferred subjects are “patients,”i.e., living humans that are receiving medical care for a disease orcondition. This includes persons with no defined illness who are beinginvestigated for signs of pathology.

Diagnosis refers to methods of estimating or determining whether or nota patient is suffering from a given disease or condition or severity ofthe condition. Diagnosis does not require ability to determine thepresence or absence of a particular disease with 100% accuracy, or eventhat a given course or outcome is more likely to occur than not.Instead, the “diagnosis” refers to an increased probability that acertain disease or condition is present in the subject compared to theprobability before the diagnostic test was performed.

Similarly, a prognosis signals an increased probability that a givencourse or outcome will occur in a patient relative to the probabilitybefore the prognostic test.

A probe or polynucleotide probe is an nucleic acid capable of binding toa target nucleic acid of complementary sequence through one or moretypes of chemical bonds, usually through complementary base pairing,usually through hydrogen bond formation, thus forming a duplexstructure. The probe binds or hybridizes to a “probe binding site.” Aprobe can include natural (i.e., A, G, C, or T) or modified bases (e.g.,7-deazaguanosine, inosine.). A probe can be an oligonucleotide which isa single-stranded DNA. Polynucleotide probes can be synthesized orproduced from naturally occurring polynucleotides. In addition, thebases in a probe can be joined by a linkage other than a phosphodiesterbond, so long as it does not interfere with hybridization. Thus, probescan include, for example, peptide nucleic acids in which the constituentbases are joined by peptide bonds rather than phosphodiester linkages(see, e.g., Nielsen et al., Science 254, 1497-1500 (1991)). Some probescan have leading and/or trailing sequences of noncomplementarityflanking a region of complementarity.

A perfectly matched probe has a sequence perfectly complementary to aparticular target sequence. The probe is typically perfectlycomplementary to a portion (subsequence) of a target sequence. The term“mismatch probe” refer to probes whose sequence is deliberately selectednot to be perfectly complementary to a particular target sequence.

The term “isolated,” “purified” or “substantially pure” means an objectspecies (e.g., a nucleic acid sequence described herein or a polypeptideencoded thereby) has been at least partially separated from thecomponents with which it is naturally associated.

Differential expression refers to a statistically significant differencein expression levels of a gene between two populations of samples (e.g.,samples with and without CAN/IFTA). The expression levels can differ forexample by at least a factor of 1.5 or 2 between such populations ofsamples. Differential expression includes genes that are expressed inone population and are not expressed (at least at detectable levels) inthe other populations. Unique expression refers to detectable expressionin one population and undetectable expression (i.e., insignificantlydifferent from background) in the other population using the sametechnique (e.g., as in the present example for detection).

Control populations for comparison with populations undergoing CAN/IFTAare usually referred to as being without CAN/IFTA. Unless otherwiseindicated, such a control population also means subjects without acutekidney rejection.

Hybridization reactions are preferably performed under stringentconditions in which probes or primers hybridize to their intended targetwith which they have perfect complementarity and not to or at least to areduced extent to other targets. An example of stringent hybridizationconditions are hybridization in 6× sodium chloride/sodium citrate (SSC)at about 45° C., followed by one or more washes in 0.2×SSC, 0.1% SDS at50° C., 55° C., 60° C., and even more or 65° C.

Statistical significance means p<0.05 or <0.01 or even <0.001 level.

DETAILED DESCRIPTION OF THE INVENTION

I. General

By a genome-wide gene analysis of expression profiles of over 50,000known or putative gene sequences in peripheral blood, the presentinventors have identified consensus sets of gene expression-basedmolecular biomarkers associated with CAN/IFTA. A set of 393 genes hasdifferential expression levels between mild chronic allograftnephropathy (CAN/IFTA) and non-rejected transplants. A set of 63 geneshave differential expression between moderate or severe CAN/IFTA andnon-rejected transplants. Additional set of protein markers showingdifferential or unique expression between CAN/IFTA and non rejectedtransplants are also provided.

II. Genes in Profiles

Table A lists 393 genes whose expression changes significantly betweenkidney transplant patients undergoing mild CAN/IFTA, Banff stage 1compared with patients not undergoing such rejection (Banff stage 0) oneyear post transplant. The columns in the table have the followingmeanings: column 1 is a number assigned to a gene, column 2 is a measureof the statistical significance of change in gene expression between theabove populations, column 3 is a mean expression level of a gene inkidney transplant patients undergoing chronic rejection (normalized asdescribed below), column 4 is mean expression level of the gene inkidney transplant patients not undergoing CAN/IFTA (similarlynormalized), column 5 is a ratio of the expression levels, column 6 isan Affymetrix number indicating a set of probes suitable for measuringexpression of the gene, column 7 is a gene name (recognized names ofHUGO or similar bodies are used when available), and column 8 is afurther description of the gene. Table B provides similar informationfor 62 genes that show differential expression between kidney transplantpatients undergoing moderate or severe CAN/IFTA (Banff stage 2 or 3)with kidney transplant patients not undergoing CAN/IFTA. Tables C and Dprovide subsets of 50 preferred genes from Tables A and B respectively.

Table E provides 117 genes and corresponding proteins for which theproteins is uniquely expressed in patients not undergoing CAN/IFTA andnot at detectable levels in patients undergoing CAN/IFTA level 1. Column1 is a sequential number for a gene/protein, column 2 is a proteinsymbol, column 3 is a gene symbol, and column 4 is a gene name. Table Fprovides similar information about 143 proteins uniquely expressed inpatients undergoing CAN/IFTA and not at detectable levels in kidneytransplant patients without CAN/IFTA. Table G provides similarinformation regarding 188 proteins that are differentially expressedbetween CAN/IFTA levels 0 and 1. The right hand column of the tableindicates the degree of differential expression with positive numbersbeing upregulated in Banff stage 1 patients. Table H provides similarinformation to Table E for 28 genes uniquely expressed in kidneytransplant patients not undergoing CAN/ITFA and not at detectable levelsin patients undergoing CAN/IFTA level 2 or 3. Table I provides similarinformation to Table F for 510 proteins uniquely expressed in CAN/IFTAlevel 2 or 3 and not detectable in kidney transplant patients notundergoing CAN/IFTA. Table J provides similar information to Table G for284 proteins differentially expressed between kidney transplant patientsat CAN/IFTA level 0 versus level 2 or 3. If a gene symbol or gene nameis not available, the protein symbol should be understood as referringto both the genes.

The genes referred to in the above tables are human genes. In somemethods, species variants or homologs of these genes are used in anon-human animal model. Species variants are the genes in differentspecies having greatest sequence identity and similarity in functionalproperties to one another. Many species variants of the above humangenes are listed in the Swiss-Prot database.

Raw gene expression levels are comparable between different genes in thesame sample but not necessarily between different samples. As notedabove, values given for gene expression levels can be normalized so thatvalues for particular genes are comparable within and between thepopulations being analyzed. The normalization eliminates or at leastreduces to acceptable levels any sample to sample differences arisingfrom factors other than CAN/IFTA (e.g. differences in overalltranscription levels of patients due to general state of health anddifferences in sample preparation or nucleic acid amplification betweensamples). The normalization effectively applies a correction factor tothe measured expression levels from a given array such that a profile ofmany expression levels in the array are the same between differentpatient samples. Software for normalizing overall expression patternsbetween different samples is both commercially and publically available(e.g., XRAY from Biotique Systems or BRB ArrayTools from the NationalCancer Institute). After applying appropriate normalizing factors to themeasured expression value of a particular gene in different samples, anaverage value of the expression level is determined for the samples in apopulation. The average values between different populations are thencompared to determine whether expression level has changed significantlybetween the populations. The changes in expression level indicated for agiven gene represent the relative expression level of that gene insamples from a population of individuals with a defined condition (e.g.,transplant patients with CAN/IFTA of specified Banff stage) relative tosamples from a control population (kidney transplant patients notundergoing CAN/IFTA). Similar principles apply in normalizing geneexpression levels at the mRNA and protein levels. Comparisons betweenpopulations are made at the same level (e.g., mRNA levels in onepopulation are compared with mRNA levels in another population orprotein levels in one population with protein levels in anotherpopulation).

III. Subject Population

The methods are particularly useful on human subjects who have undergonea kidney transplant although can also be used on subjects who have goneother types of transplant (e.g., heart, liver, lungs, stem cell) or onnon-humans who have undergone kidney or other transplant. Geneexpression levels in such subjects can be measured, for example, within,three months, six months, one year, two years, five years or ten yearsafter a kidney transplant. In some methods, gene expression levels aredetermined at regular intervals, e.g., every 3 months, 6 months or everyyear posttransplant, either indefinitely, or until evidence of CAN/IFTAis observed, in which case the frequency of monitoring is sometimesincreased. In some methods, baseline values of expression levels aredetermined in a subject before a kidney transplant in combination withdetermining expression levels at one or more time points thereafter. Inother methods, a measurement is initiated responsive to some otherindication of potential kidney impairment, such as a rise in levels ofcreatinine or BUN or a decrease in glomerular filtration rate. Similarmethods can be practiced in non-human species, in which cases, theexpression levels measured are the species equivalent of the human genesreferenced above.

IV. Chronic Allograft Nephropathy (Can/IFTA) and its Subtypes

The methods are particularly useful for detecting CAN/IFTA. CAN/IFTA canbe further classified by histological analysis of kidney transplantbiopsies based on the Banff 2007 schema and the following four subtypesor stages are recognized indicating severity: 0 (no CAN/IFTA), 1 (mildCAN/IFTA), 2 (moderate CAN/IFTA) and 3 (severe CAN/IFTA) [4]. Analternative and complementary histology grading schema is the ChronicAllograft Damage Index (CADI) score and this score is often provided bypathologists with the Banff classification score as supplementalinformation (for example, see Yilmaz et al, J Am Soc Nephrol 2003 14:773-779). There is also a Banff 2007 classification for acute rejection[4]. Acute rejection is characterized histologically by an active,inflammatory/immune cell infiltration comprised of various numbers of Tcells and B cells as well as sometimes plasma cells, eosinophils,neutrophils and macrophages.

V. Methods of Measuring Profiles

The preferred sample type for analysis is a blood sample, which refersto whole blood or fractions thereof, such as plasma, or lymphocytes.Other samples that can be analyzed include urine, feces, saliva, and akidney biopsy. The samples are typically isolated from a subject,particularly as a peripheral blood sample, and not returned to thesubject. The analytes of interests in the samples can be analyzed withor without further processing of the sample, such as purification andamplification. Samples not requiring biopsy to obtain, particularlyperipheral blood, are preferred.

Expression profiles are preferably measured at the nucleic acid level,meaning that levels of mRNA or nucleic acid derived therefrom (e.g.,cDNA or cRNA). An expression profile refers to the expression levels ofa plurality of genes in a sample. A nucleic derived from mRNA means anucleic acid synthesized using mRNA as a template. Methods of isolationand amplification of mRNA are well known as described for example WO97/10365, WO 97/27317, Chapter 3 of Laboratory Techniques inBiochemistry and Molecular Biology Hybridization With Nucleic AcidProbes, Part I. Theory and Nucleic Acid Preparation, (P. Tijssen, ed.)Elsevier, N.Y. (1993). If mRNA or a nucleic acid therefrom is amplified,the amplification is performed under conditions that approximatelypreserve the relative proportions of mRNA in the original samples, suchthat the levels of the amplified nucleic acids can be used to establishphenotypic associations representative of the mRNAs.

A variety of approaches are available for determining mRNA levelsincluding probe arrays and quantitative PCR. A number of distinct arrayformats are available. Some arrays, such as an Affymetrix GeneChip®array, have different probes occupying discrete known areas of acontiguous support. Other arrays, such as arrays from Illumina, havedifferent probes attached to different particles or beads. In sucharrays, the identity of which probe is attached to which particle orbeads is usually determinable from an encoding system. The probes can beoligonucleotides. In such case, typically several match probes areincluded with perfect complementarity to a given target mRNA together,optionally together with mismatch probes differing from the match probesare a known number of oligonucleotides (Lockhart, et al., NatureBiotechnology 14:1675-1680 (1996); and Lipschutz, et al., NatureGenetics Supplement 21: 20-24, 1999). Other arrays including full lengthcDNA sequences with perfect or near perfect complementarity to aparticular cDNA (Schena et al. (Science 270:467-470 (1995); and DeRisiet al. (Nature Genetics 14:457-460 (1996)). Such arrays can also includevarious control probes, such as a probe complementarity with a housekeeping gene likely to be expressed in most samples. Regardless of thespecifics of array design, an array contains one or more probes eitherperfectly complementary to a particular target mRNA or sufficientlycomplementarity to the target mRNA to distinguish it from other mRNAs inthe sample, and the presence of such a target mRNA can be determinedfrom the hybridization signal of such probes, optionally by comparisonwith mismatch or other control probes included in the array. Typically,the target bears a fluorescent label, in which case hybridizationintensity can be determined by, for example, a scanning confocalmicroscope in photon counting mode. Appropriate scanning devices aredescribed by e.g., U.S. Pat. No. 5,578,832, and U.S. Pat. No. 5,631,734.The intensity of labeling of probes hybridizing to a particular mRNA orits amplification product provides a raw measure of expression level.

In other methods, expression levels are determined by so-called “realtime amplification” methods also known as quantitative PCR or Taqman(see, e.g., U.S. Pat. No. 5,210,015 to Gelfand, U.S. Pat. No. 5,538,848to Livak, et al., and U.S. Pat. No. 5,863,736 to Haaland, as well asHeid, C. A., et al., Genome Research, 6:986-994 (1996); Gibson, U. E. M,et al., Genome Research 6:995-1001 (1996); Holland, P. M., et al., Proc.Natl. Acad. Sci. USA 88:7276-7280, (1991); and Livak, K. J., et al., PCRMethods and Applications 357-362 (1995)). The basis for this method ofmonitoring the formation of amplification product is to measurecontinuously PCR product accumulation using a dual-labeled fluorogenicoligonucleotide probe. The probe used in such assays is typically ashort (ca. 20-25 bases) polynucleotide that is labeled with twodifferent fluorescent dyes. The 5′ terminus of the probe is typicallyattached to a reporter dye and the 3′ terminus is attached to aquenching dye The probe is designed to have at least substantialsequence complementarity with a site on the target mRNA or nucleic acidderived from. Upstream and downstream PCR primers that bind to flankingregions of the locus are also added to the reaction mixture. When theprobe is intact, energy transfer between the two fluorophors occurs andthe quencher quenches emission from the reporter. During the extensionphase of PCR, the probe is cleaved by the 5′ nuclease activity of anucleic acid polymerase such as Taq polymerase, thereby releasing thereporter from the polynucleotide-quencher and resulting in an increaseof reporter emission intensity which can be measured by an appropriatedetector. The recorded values can then be used to calculate the increasein normalized reporter emission intensity on a continuous basis andultimately quantify the amount of the mRNA being amplified. mRNA levelscan also be measured without amplification by hybridization to a probe,for example, using a branched nucleic acid probe, such as a QuantiGene®Reagent System from Panomics.

Alternatively or additionally, expression levels of genes can bedetermined at the protein level, meaning that levels of proteins encodedby the genes discussed above are measured. Several methods and devicesare well known for determining levels of proteins including immunoassayssuch as described in e.g., U.S. Pat. Nos. 6,143,576; 6,113,855;6,019,944; 5,985,579; 5,947,124; 5,939,272; 5,922,615; 5,885,527;5,851,776; 5,824,799; 5,679,526; 5,525,524; and 5,480,792. These assaysinclude various sandwich, competitive, or non-competitive assay formats,to generate a signal that is related to the presence or amount of anprotein analyte of interest. Any suitable immunoassay may be utilized,for example, lateral flow, enzyme-linked immunoassays (ELISA),radioimmunoassays (RIAs), competitive binding assays, and the like.Numerous formats for antibody arrays have been described proposedemploying antibodies. Such arrays typically include different antibodieshaving specificity for different proteins intended to be detected. Forexample, usually at least one hundred different antibodies are used todetect one hundred different protein targets, each antibody beingspecific for one target. Other ligands having specificity for aparticular protein target can also be used, such as the syntheticantibodies disclosed in WO/2008/048970. Other compounds with a desiredbinding specificity can be selected from random libraries of peptides orsmall molecules. U.S. Pat. No. 5,922,615 describes a device thatutilizes multiple discrete zones of immobilized antibodies on membranesto detect multiple target antigens in an array. U.S. Pat. Nos.5,458,852, 6,019,944, U.S. Pat. No. 6,143,576. Microtiter plates orautomation can be used to facilitate detection of large numbers ofdifferent proteins. Protein levels can also be determined by massspectrometry as described in the examples.

The selection of genes for determination of expression levels depends onthe particular application (e.g., analysis of CAN/IFTA in general or oneof the subtypes described above). In general, the genes are selectedfrom one of the tables indicated above as appropriate for theapplication. In some methods, expression levels of at least 2, 3, 4, 5,10, 20, 25, 50, 100, 150, 250 (e.g. 100-250) genes shown in any of TableA, B, C or D are determined. In some methods, expression levels of atleast 2, 3, 4, 5, 10, 20, 25, 50, 100, 150, 250 or all genes shown inTable A are determined and/or expression levels of 2, 3, 4, 5, 10, 20,25, 50 or all genes shown in Table B are determined. In some methods,expression levels of at least 2, 3, 4, 5, 10, 20, 25, or all 50 genes inTable C and at least 2, 3, 4, 5, 10, 20, 25, or all 50 genes in Table Dare determined. In some methods, expression levels of 2, 3, 4, 5, 10,20, 25, 50 or all genes shown in Tables 2, 3, 4, 5 and/or 6 aredetermined (genes for which both mRNAs and proteins are differentiallyexpressed). In some methods, all genes are from the same table (i.e.,all genes with differential expression associated with mild CAN/IFTA).In some methods, genes from different tables (i.e., including genesassociated with mild CAN/IFTA and moderate/severe CAN/IFTA) are tested.In some methods, genes are selected such that genes from severaldifferent pathways are represented (e.g., at least one gene from atleast 2, 3, 5, or 10 pathways, such as those described in the Examples).The genes within a pathway tend to be expressed in a co-ordinatedexpression whereas genes from different pathways tend to be expressedmore independently. Thus, changes in expression based on the aggregatechanges of genes from different pathways can have greater statisticalsignificance than aggregate changes of genes within a pathway.

In some methods, expression levels of at least 2, 3, 4, 5, 10, 20, 25,50, 100, or 150 proteins or corresponding genes shown in any of TablesE, F, G, H, I and/or J are determined. In some methods, expressionlevels of at least 2, 3, 4, 5, 10, 20, 25, 50, 100, 150 or all proteinsor genes shown in Table E, F, and/or G are determined and/or expressionlevels of 2, 3, 4, 5, 10, 20, 25, 50 or all proteins or genes shown inTables H, I and/or J are determined. In some methods, proteins or genesare selected from the same table (e.g., proteins uniquely expressed inBanff stage 1, or corresponding genes). In some methods, proteins orgenes are selected from two tables (e.g., proteins uniquely expressed inBanff stage 0 (or corresponding genes) and proteins uniquely expressedin Banff stage 1 (or corresponding genes). In some methods, proteins orgenes are selected from three tables (e.g., proteins uniquely expressedin Banff stage 0 or corresponding genes, proteins uniquely expressed inBanff stage 1 and corresponding genes, and proteins differentiallyexpressed between Banff stages 1 and 0. Analogous selections of proteinscan be made from Tables H-J for purposes of distinguishing Banff stages0 and 2/3. In some methods, proteins or corresponding genes are selectedsuch that proteins from several different pathways are represented(e.g., at least one gene from at least 2, 3, 5, or 10 pathways, such asthose described in the Examples).

Expression levels of the present genes and/or proteins can be combinedwith or without determination of expression levels of any other genes orproteins of interest (e.g., genes or proteins associated with rejectionof kidneys or other organs in WO 2007/104537, WO 2009/060035),Anglicheau et al., PNAS 106, 5330-5335 (2009)) and references, 16, 20,21, 22, 23, 25, 26, 37 and 39. In some methods, the gene is not DPYD orIRS2 or the method includes determining the expression level of at least5, 10, 25 or 50 genes other than DPYD and IRS2.

Regardless of the format adopted, the present methods can (but need not)be practiced by detection expression levels of a relatively small numberof genes or proteins compared with the whole genome level expressionanalysis described in the Examples. In some methods, the total number ofgenes whose expression levels are determined is less than 5000, 1000,500, 200, 100, 50, 25, 10, 5 or 3. In some methods, the total number ofgenes whose expression level is determined is 100-1500, 100-250,500-1500 or 750-1250. In some methods, the total number of proteinswhose expression levels are determined is less than 5000, 1000, 500,200, 100, 50, 25, 10, 5 or 3. In some methods, the total number ofproteins whose expression level is determined is 100-1500, 100-250,500-1500 or 750-1250. Correspondingly, when an array form is used fordetection of expression levels, the array includes probes or probes setsfor less than 5000, 1000, 500, 200, 100, 50, 25, 10, 5 or 3 genes. Thus,for example, an Affymetrix GeneChip® expression monitoring arraycontains a set if about 20-50 oligonucleotide probes (half match andhalf-mismatch) for monitoring each gene of interest. Such an arraydesign would include less than 5000, 1000, 500, 200, 100, 50, 25, 10, 5or 3 such probes sets for detecting less than 5000, 1000, 500, 200, 100,50, 25, 10, 5 or 3 genes. By further example, an alternative arrayincluding one cDNA for each gene whose expression level is to bedetected would contain less than 5000, 1000, 500, 200, 100, 50, 25, 10,5 or 3 such cDNAs for analyzing less than 5000, 1000, 500, 200, 100, 50,25, 10, 5 or 3 genes. By further example, an array containing adifferent antibody for each protein to be detected would containing lessthan 5000, 1000, 500, 200, 100, 50, 25, 10, 5 or 3 different antibodiesfor analyzing less than 5000, 1000, 500, 200, 100, 50, 25, 10, 5 or 3gene products.

VI. Analysis of Expression Levels

Analysis of expression levels initially provides a measurement of theexpression level of each of several individual genes. The expressionlevel can be absolute in terms of a concentration of an expressionproduct, or relative in terms of a relative concentration of anexpression product of interest to another expression product in thesample. For example, relative expression levels of genes can beexpressed with respect to the expression level of a house-keeping genein the sample. Relative expression levels can also be determined bysimultaneously analyzing differentially labeled samples hybridized tothe same array. Expression levels can also be expressed in arbitraryunits, for example, related to signal intensity.

The individual expression levels, whether absolute or relative, can beconverted into values or other designations providing an indication ofpresence or risk of CAN/IFTA by comparison with one or more referencepoints. The principles are first discussed with respect to CAN/IFTAwithout regarding to subtype. However, the same principles apply foranalysis of subtypes except that the gene sets used may be different.For example, mild CAN/IFTA can be determined using genes or proteinsfrom Tables A, C, E, F and/or G. Mid to severe CAN/IFTA can be determineusing genes or proteins from Tables B, D, H, I and/or J. Genes orproteins from any of the tables can be used in analyzing CAN/IFTAwithout regard to subtype. Preferably, genes in both Tables A/C and B/Dor proteins occurring in at least one of Tables E-G and at least one ofTables H-J are used for such analysis. Genes or proteins are found inboth Banff 1 and Banff 2,3 CAN/IFTA but not found in Banff 0 are alsouseful in distinguishing the presence of CAN/IFTA in a patient. Acombination of genes and/or proteins associated with mild CAN/IFTA andgenes and/or proteins associated with mid to severe CAN/IFTA can beused.

The reference points can include a measure of an average expressionlevel of a gene in subjects having had a kidney transplant withoutCAN/IFTA, and/or an average value of expression levels in subjectshaving had a kidney transplant with CAN/IFTA. The reference points canalso include a scale of values found in kidney transplant patientsincluding patients having and not having CAN/IFTA. The reference pointscan also or alternatively include a reference value in the subjectbefore kidney transplant, or a reference value in a population of apatients who have not undergone kidney transplant. Such reference pointscan be expressed in terms of absolute or relative concentrations of geneproducts as for measured values in a sample.

For comparison between a measured expression level and referencelevel(s), the measured level sometimes needs to be normalized forcomparison with the reference level(s) or vice versa. The normalizationserves to eliminate or at least minimize changes in expression levelunrelated to CAN/IFTA (e.g., from differences in overall health of thepatient or sample preparation). Normalization can be performed bydetermining what factor is needed to equalize a profile of expressionlevels measured from different genes in a sample with expression levelsof these genes in a set of reference samples from which the referencelevels were determined. Commercial software is available for performingsuch normalizations between different sets of expression levels.

Comparison of the measured expression level of a gene with one or moreof the above reference points provides a value (i.e., numerical) orother designation (e.g., symbol or word(s)) of presence orsusceptibility to CAN/IFTA. In some methods, a binary system is used;that is a measured expression level of a gene is assigned a value orother designation indicating presence or susceptibility to CAN/IFTA orlack thereof without regard to degree. For example, the expression levelcan be assigned a value of 1 to indicate presence or susceptibility toCAN/IFTA and −1 to indicate absence or lack of susceptibility toCAN/IFTA. Such assignment can be based on whether the measuredexpression level is closer to an average level in kidney transplantpatients having or not having CAN/IFTA. In other methods, a ternarysystem is used in which an expression level is assigned a value or otherdesignation indicating presence or susceptibility to CAN/IFTA or lackthereof or that the expression level is uninformative. Such assignmentcan be based on whether the expression level is closer to the averagelevel in kidney transplant patient undergoing CAN/IFTA, closer to anaverage level in kidney transplant patients lacking CAN/IFTA orintermediate between such levels. For example, the expression level canbe assigned a value of +1, −1 or 0 depending on whether it is closer tothe average level in patients undergoing CAN/IFTA, is closer to theaverage level in patients not undergoing CAN/IFTA or is intermediate. Inother methods, a particular expression level is assigned a value on ascale, where the upper level is a measure of the highest expressionlevel found in kidney transplant patients and the lowest level of thescale is a measure of the lowest expression level found in kidneytransplant patients at a defined time point at which patients may besusceptible to CAN/IFTA (e.g., one year post transplant). Preferably,such a scale is normalized scale (e.g., from 0-1) such that the samescale can be used for different genes. Optionally, the value of ameasured expression level on such a scale is indicated as being positiveor negative depending on whether the upper level of the scale associateswith presence or susceptibility to CAN/IFTA or lack thereof. It does notmatter whether a positive or negative sign is used for chronic ejectionor lack thereof as long as the usage is consistent for different genes.

Values or other designation can also be assigned based on a change inexpression level of a gene relative to a previous measurement of theexpression level of gene in the same patient. Here as elsewhereexpression level of a gene can be measured at the protein or nucleicacid level. Such a change can be characterized as being toward, awayfrom or neutral with respect to average expression levels of the gene inkidney transplant patients undergoing or not undergoing CAN/IFTA. Forexample, a gene whose expression level changes toward an averageexpression level in kidney transplant patients undergoing CAN/IFTA canbe assigned a value of 1 and a gene whose express level changes way froman average expression level in kidney transplant patients undergoingCAN/IFTA and toward an average expression level in kidney transplantpatients not undergoing CAN/IFTA can be assigned a value −1. Of course,more sophisticated systems of assigning values are possible based on themagnitude of changes in expression of a gene in a patient.

Having determined values or other designations of expression levels ofindividual genes providing an indication of presence or susceptibilityto chronic ejection or lack thereof, the values or designations arecombined to provide an aggregate value for all of the genes beinganalyzed. If each gene is assigned a score of +1 if its expression levelindicates presence or susceptibility to CAN/IFTA and −1 if itsexpression level indicates absence or lack of susceptibility to CAN/IFTAand optionally zero if uninformative, the different values can becombined by addition. The same approach can be used if each gene isassigned a value on the same normalized scale and assigned as beingpositive or negative depending whether the upper point of the scale isassociate with presence or susceptibility to CAN/IFTA or lack thereof.Other methods of combining values for individual markers of disease intoa composite value that can be used as a single marker are described inUS20040126767 and WO/2004/059293.

VII. Subtyping

CAN/IFTA can be classified into three subtypes, mild, mid and severe bythe Banff scheme. These subtypes differ by histology and severity. Thesubtypes can be distinguished by the same principles and strategy asjust discussed for presence or absence of CAN/IFTA, except that the setof genes whose expression levels is determined may be different forpresence and absence of CAN/IFTA overall and each of the subtypes asindicated above. In some methods, one first analyzes CAN/IFTAindependent of subtype and then looks at profiles of one or more sets ofgenes characteristic of one of the above subtypes. In some methods,detection of CAN/IFTA and subtypes are performed simultaneously, forexample, by including probes for the sets of genes required for eachanalysis on the same array. In other methods, analysis of multiplesubtypes is performed sequentially or simultaneously and analysis ofoverall CAN/IFTA is performed by aggregating the results from thedifferent subtypes.

The principles for subtyping are closely analogous to those foranalyzing CAN/IFTA independent of subtype. For example, to analyzewhether mild CAN/IFTA is present, one determines expression levels of aset of genes whose expression levels are characterized of this subtype(Tables A, C, E, F and/or G). The measured expression levels are thencompared with one or more reference levels of the genes. The referencelevels can, for example, represent an average expression level of a genein kidney transplant patients undergoing mild CAN/IFTA with borderlinephenotype and an average expression level of the gene in kidneytransplant patients not undergoing any kidney rejection, an averageexpression level of the gene in kidney transplant patients undergoingCAN/IFTA of a different subtype, or an earlier measurement of expressionlevel of the gene in the same patient. The same principles are used foranalyzing combined moderate/severe CAN/IFTA except that the set of genesis selected from Tables B, D, H, I and/or J and the reference levelsrepresent an average expression level of a gene in transplant patientsundergoing CAN/IFTA with Banff subtype 2 or 3, an average expressionlevel of the gene in kidney transplant patients not undergoing kidneyrejection of any kind, an average expression level of the gene in kidneytransplant patients undergoing CAN/IFTA of a different subtype, or anearlier measurement of expression level of the gene in the same patient.

If subtyping is performed for both mild CAN/IFTA and moderate/severeCAN/IFTA, the aggregate of the results also indicates overall CAN/IFTA.For example, if the patient is assigned a value or other designationindicating absence or relatively low risk of developing mild CAN/IFTAand a value or other designation indicating absence or relatively lowrisk of developing moderate/severe CAN/IFTA, then the patient is alsoindicated as having absence of overall CAN/IFTA and/or a relatively lowrisk of developing the same. Conversely, if the patient is assigned avalue or other designation indicating presence or enhanced risk toeither mild CAN/IFTA or mid/severe CAN/IFTA, or both, the patients isalso indicated as having presence or enhanced risk of overall CAN/IFTA.

VIII. Diagnosis, Prognosis and Monitoring

The above described methods can provide a value or other designation fora patient which indicates whether the aggregate measured expressionlevels in a patient is more like kidney transplant patients with orwithout CAN/IFTA or a subtype thereof. Such a value provides anindication that the patient either has or is at enhanced risk ofCAN/IFTA or a subtype thereof, or conversely does not have or is atreduced risk of CAN/IFTA or a subtype thereof. Risk is a relative termin which risk of one patient is compared with risk of other patientseither qualitatively or quantitatively. For example, the a value of onepatient can be compared with a scale of values for a population ofpatients having undergone kidney transplant to determine whether thepatient's risk relative to that of other patients. In general, diagnosisis the determination of the present condition of a patient (e.g.,presence or absence of CAN/IFTA) and prognosis is developing futurecourse of the patient (e.g., risk of developing CAN/IFTA in the futureor likelihood of improvement in response to treatment); however, theanalyses contemplated by these terms may overlap or even be the same.For example, the present methods alone do not necessarily distinguishbetween presence and enhanced risk of CAN/IFTA or a subtype thereof.However, these possibilities can be distinguished by additional testing.

If a patient is indicated as having or being at enhanced risk ofCAN/IFTA or a subtype thereof, the physician can subject the patient toadditional testing including performing a kidney biopsy or performingother analyses such as creatinine, BUN or glomerular filtration rate atincreased frequency. Additionally or alternatively, the physician canchange the treatment regime being administered to the patient. A changein treatment regime can include administering an additional or differentdrug, or administering a higher dosage or frequency of a drug alreadybeing administered to the patient. Many different drugs are availablefor treating rejection, such as immunosuppressive drugs used to treattransplant rejection calcineurin inhibitors (e.g., cyclosporine,tacrolimus), mTOR inhibitors (e.g., sirolimus and everolimus),anti-proliferatives (e.g., azathioprine, mycophenolic acid),corticosteroids (e.g., prednisolone and hydrocortisone) and antibodies(e.g., basiliximab, daclizumab, Orthoclone, anti-thymocyte globulin andanti-lymphocyte globulin). Conversely, if the value or other designationof aggregate expression levels of a patient indicates the patient doesnot have or is at reduced risk of CAN/IFTA, the physician need not orderfurther diagnostic procedures, particularly not invasive ones such asbiopsy. Further, the physician can continue an existing treatmentregime, or even decrease the dose or frequency of an administered drug.

In some methods, expression levels are determined at intervals in aparticular patient (i.e., monitoring). Such methods can provide a seriesof values changing over time indicating whether the aggregate expressionlevels in a particular patient are more like the expression levels inpatients undergoing CAN/IFTA or not undergoing CAN/IFTA. Movement invalue toward or away from CAN/IFTA or a subtype can provide anindication whether an existing immunosuppressive regime is working,whether the immunosuppressive regime should be changed or whether abiopsy or increased monitoring by markers such as creatinine orglomerular filtration rate should be performed.

Information from subtyping analysis can provide further guidance inwhether to perform additional diagnostic measures and/or change theimmunosuppressive regime administered to a subject. For example,presence or risk of subtype 2 or 3 is more suggestive of performing anadditional diagnostic procedure (e.g., biopsy) and/or increasing therigor of an immunosuppressive regime that is the presence or risk ofsubtype 1.

IX. Drug Screening

The expression profiles associated with CAN/IFTA (including subtypes) orlack thereof provided by the invention are useful in screening drugs,either in clinical trials or in animal models of CAN/IFTA. A clinicaltrial can be performed on a drug in similar fashion to the monitoring ofa individual patient described above, except that drug is administeredin parallel to a population of kidney transplant patients, usually incomparison with a control population administered a placebo.

The changes in expression levels of genes can be analyzed in individualpatients and across a treated or control population. Analysis at thelevel of an individual patient provides an indication of the overallstatus of the patient at the end of the trial (i.e., whether geneexpression profile indicates presence or enhanced susceptibility toCAN/IFTA) and/or an indication whether that profile has changed towardor away from such indication in the course of the trial. Results forindividual patients can be aggregated for a population allowingcomparison between treated and control population.

Similar trials can be performed in non-human animal models of chronickidney disease, e.g., the mouse model of Mannon et al., KidneyInternational (1999) 55, 1935-1944 In this case, the expression levelsof genes detected are the species variants or homologs of the humangenes referenced above in whatever species of non-human animal on whichtests are being conducted. Although the average expression levels ofhuman genes determined in human kidney transplant patients undergoing ornot undergoing CAN/IFTA are not necessarily directly comparable to thoseof homolog genes in an animal model, the human values can neverthelessbe used to provide an indication whether a change in expression level ofa non-human homolog is in a direction toward or away from CAN/IFTA orsusceptibility thereto. The expression profile of individual animals ina trial can provide an indication of the status of the animal at the endof the trial with respect to presence or susceptibility to CAN/IFTAand/or change in such status during the trial. Results from individualanimals can be aggregated across a population and treated and controlpopulations compared. Average changes in the expression levels of genescan then be compared between the two populations.

X. Computer Implemented Methods

Expression levels can be analyzed and associated with status of asubject (e.g., presence or susceptibility to chronic kidney infection)in a digital computer. Optionally, such a computer is directly linked toa scanner or the like receiving experimentally determined signalsrelated to expression levels. Alternatively, expression levels can beinput by other means. The computer can be programmed to convert rawsignals into expression levels (absolute or relative), compare measuredexpression levels with one or more reference expression levels, or ascale of such values, as described above. The computer can also beprogrammed to assign values or other designations to expression levelsbased on the comparison with one or more reference expression levels,and to aggregate such values or designations for multiple genes in anexpression profile. The computer can also be programmed to output avalue or other designation providing an indication of presence orsusceptibility to CAN/IFTA as well as any of the raw or intermediatedata used in determining such a value or designation.

A typically computer (see U.S. Pat. No. 6,785,613 FIGS. 4 and 5)includes a bus which interconnects major subsystems such as a centralprocessor, a system memory, an input/output controller, an externaldevice such as a printer via a parallel port, a display screen via adisplay adapter, a serial port, a keyboard, a fixed disk drive and afloppy disk drive operative to receive a floppy disk. Many other devicescan be connected such as a scanner via I/O controller, a mouse connectedto serial port or a network interface. The computer contains computerreadable media holding codes to allow the computer to perform a varietyof functions. These functions include controlling automated apparatus,receiving input and delivering output as described above. The automatedapparatus can include a robotic arm for delivering reagents fordetermining expression levels, as well as small vessels, e.g.,microtiter wells for performing the expression analysis.

EXAMPLES

Materials and Methods:

Patient Populations: Test Set 1 comprised 42 kidney transplant patientsrandomized to either cyclosporine or de novo rapamycin at the ClevelandClinic, whose clinical courses have been previously, described[15,16,24]. Density gradient-purified peripheral blood lymphocytes (PBL)were collected at the time of protocol two-year biopsies. Test Set 2comprised 35 patients from 3 clinical centers (St. Vincent's MedicalCenter, Scripps Clinic, and Cleveland Clinic). All patients were onFK506. Whole blood was collected directly into PaxGene Tubes(PreAnalytix) at the time of biopsies for suspected CAN/IFTA or protocolone-year biopsies. All the studies in this manuscript were covered byHuman Subjects Research Protocols approved by each Center'sInstitutional Review Board and by the IRB of The Scripps ResearchInstitute as the parent institution. Informed consent was obtained fromall study subjects in the study.

Pathology: Banff IF/TA grades based on tubulointerstitial features weredetermined for all patients by kidney biopsies: grade 0 (no evidenceCAN/IFTA), 1 (mild CAN/IFTA), and 2 (moderate CAN/IFTA) and 3 (severeCAN/IFTA). We merged patients with Banff 2 and Banff 3 IF/TA to increasenumbers. Diagnosis was done first by local pathologists and reviewed ina blinded fashion. C4d staining was only available in the more recentlyacquired Test Set 2.

Gene expression profiling and analysis: RNA was extracted from Test Set1 using Trizol (Invitrogen) and in Test Set 2 using Paxgene Blood RNAsystem (PreAnalytix) and globin transcripts were reduced usingGlobinClear (Ambion). Biotinylated cRNA was prepared using AmbionMessageAmp Biotin II (Ambion) and hybridized to Affymetrix Human GenomeU133 Plus 2.0 GeneChips. Normalized signals that were generated using aquantile normalization strategy (RMAExpress[25]) were used for classcomparisons (ANOVA) and class predictions (BRB Array Tools;linus.nci.nih.gov/BRB-ArrayTools.html). We chose the Diagonal LinearDiscriminant Analysis (DLDA) method for class predictions, which isbased on maximum likelihood discriminant rules that give consistentlygood results with our data set and others[26]. Receiver OperatingCharacteristics (ROC) analysis was done using JROCFIT(rad.jhmi.edu/jeng/javarad/roc/JROCFITi.html). Heatmaps were generatedusing Cluster and Treeview[27] and functional analysis was performedusing Gene Ontology (GO) (geneontology.org/) and Ingenuity PathwayAnalysis (IPA). Consensus analysis was designed to identify trueclassifiers in the two independently collected data sets. Variabilitybetween the two test sets within each class (i.e. Banff 1/Test Set 1 vs.Banff 1/Test Set 2) was eliminated by removing all genes with aStudent's t-test p-value of <0.05 after which the remaining genes wereused to identify consensus candidates by class comparisons. All themicroarray data for this study is available for review at the privateGEO accession sitencbi.nlm.nih.gov/geo/query/acc.cgi?token=vbgvzkwuggqiqpy&acc=GSE12187.

Shotgun LC/MS/MS proteomics: All protein samples were prepared fromdensity gradient-purified PBL. Individual patient samples were pooledwithin each Test Set (3 samples/pool) based on Banff classifications andpools were run in triplicates. Total protein was proteolyticallydigested with trypsin and samples run using Multidimensional ProteinIdentification Tool (MudPIT) protocol as previously described[28] usingan LTQ XL mass spectrometer (ThermoFisher). Raw data were searchedagainst the EBI-IPI_human_12_01_2006 database supplemented with a decoydatabase where each entry of the original protein contains its reversedsequence. Database searching used SEQUEST (v27)[29] and outcomes werefiltered using DTASelect[30]. Relative quantifications were done usingspectral counts nothialized to the median of the total spectralcounts[31]. Pair-wise comparisons between CAN/IFTA biopsy classes weredone by differentially expressed proteins (Student's t-test, p≦0.05) andas all-or-none/unique events.

Results:

Study Population

Recipients in both Test Sets were sex and age matched (Table 1). Theonly significant differences in Test Set 1 were Donor age between Banff0 and Banff 1 groups. In Test Set 2 there were significant differencesin induction therapy between Banff 0 and Banff 1 and between Banff 0 andthe Banff 2,3; time to biopsy between Banff 0 and Banff 1 and betweenBanff 0 and the Banff 2,3; and steroid use between Banff 0 and Banff 1and between Banff 0 and Banff 2,3. Only the Banff 2,3 group in Test Set2 had a significantly higher serum creatinine compared to the Banff 0,thus, renal function levels per se were not a major determinant of thegene profiles. The higher creatinine levels in the Banff 2,3 group ofTest Set 2 most likely reflect the fact that this group was “biopsy forcause,” whereas Test Set 1 were all protocol biopsies done regardless ofany renal function change. However, by design, the two Test Setsdiffered significantly in recipient age, HLA mismatch, inductiontherapy, clinical center, immunosuppression, serum creatinines, and timeto biopsy.

Gene Expression Profiling of Mild CAN/IFTA

We performed ANOVA-based class comparisons between Banff 0 (nohistological evidence of CAN/IFTA) and Banff 1 (mild CAN/IFTA). Atp-values<0.005, 1066 genes (1307 probe sets) were differentiallyexpressed. Annotation of function by Gene Ontology (GO) shows 8categories comprised of >25 genes each including 58 genes linked toimmunity and inflammation. The percentage of genes in each category wasimmune/inflammatory 5%, apoptosis, 4%, cell adhesion 3%, signaltransduction 5%, regulation of transcription 6%, protein phosphorylation3%, cell cycle 3%, metabolism 11%, other functions 40%, unknownfunctions 20%. IPA shows that these 1066 genes fall into 27 networkswith >15 genes per network. The top network was immune response and twoadditional networks in the top 10 were also immune response with 27 and22 focus genes, respectively. The top canonical pathway was Toll-likeReceptor Signaling followed by SAPK/JNK, Apoptosis, Notch and DeathReceptor and Interferon Signaling. Finding 1066 significantlydifferentially expressed genes is a first indication that PBL transcriptprofiling is capable of classifying subjects defined by CAN/IFTA biopsyhistology. Class prediction using DLDA demonstrates 90% mean correctclassification[32,33]. Supervised hierarchical clustering showsmisclassification of only 2 samples.

Based on gene expression profiles of the whole blood samples in Test Set2, there were 1429 genes (1591 probe sets) differentially expressed atp-values<0.005. GO annotation of gene functions revealed the same groupsas PBL including 50 immune response genes. The percentage of genes ineach category was immune/inflammatory 4%, apoptosis, 2%, cell adhesion2%, signal transduction 8%, regulation of transcription 6%, proteinphosphorylation 1%, cell cycle 1%, metabolism 4%, other functions 35%,unknown functions 37%. IPA reveals 30 networks with ≧15 genes pernetwork. The top canonical pathways were: B Cell Receptor, Toll-likeReceptor, Death Receptor, Chemokine, Glucocorticoid Receptor, and IL-4Signaling. DLDA demonstrates 88% mean correct classification. Supervisedhierarchical clustering shows misclassification of only 1 sample.

A consensus analysis for Banff 0 vs. Banff 1 was performed with thesetwo independently collected data sets by a class comparison atp-values<0.005 and identified 393 genes (424 probe sets) significantlydifferentially expressed in both data sets. This “consensus” gene listrepresents the intersection of these two significantly different testsets classifying mild CAN/IFTA by blood transcription profiling. We thencombined all the samples of both Test Sets (n=55) and performed classpredictions using the top 50 differentially expressed, consensus genesranked by p values to obtain a class prediction accuracy of 80% depictedas a ROC curve (FIG. 1). A heat map classifying Banff 0 vs. Banff 1using the 50 genes shows there are large “blocks” of up- ordown-regulated genes that classify the Banff 0 vs. Banff 1 (mildCAN/IFTA). However, signatures of multiple genes are advantageous toachieve high class predictive accuracies in heterogeneous clinicalpopulations that are the reality of transplantation medicine. We tookthe top 10 and top 3 genes from our consensus set for mild CAN/IFTA andperformed class prediction using the DLDA method. The top 10 had apredictive accuracy of 80%, sensitivity of 85% and specificity of 77%,whereas the top 3 genes had a predictive accuracy of 80%, sensitivity of74% and specificity of 86%.

Gene Expression Profiling of Moderate/Severe CAN/IFTA

Class comparisons between Banff 0 and Banff 2,3 identified genesdifferentially expressed between patients without CAN/IFTA and thosewith moderate to severe CAN/IFTA. In Test Set 1, 172 genes weredifferentially expressed (p<0.005) and classified the samples by DLDAwith 78% accuracy. In Test Set 2 there were 545 differentially expressedgenes. DLDA classified 95% of the samples accurately. The percentage ofgenes in each category for sets 1 and 2 was immune/inflammatory 4%, 3%,apoptosis, 2%, 3%, cell adhesion 2%, 3%, signal transduction 8%, 7%,regulation of transcription 6%, 8%, protein phosphorylation 1%, 3%, cellcycle 1%, 1%, metabolism 4%, 6% other functions 33%, 30%, unknownfunctions 37%, 36%. A consensus analysis was done as already describedto yield 62 differentially expressed genes (p<0.005) shared for bothTest Sets of moderate/severe CAN/IFTA (n=49). The ROC curve for the top50 genes from this consensus gene set shows a class prediction accuracyof 92% (FIG. 2).

Proteomic Expression of Mild and Moderate/Severe CAN/IFTA

To investigate using proteomics to define blood cell biomarkers forCAN/IFTA, we performed shotgun tandem mass spectrometry. All samplesrepresented purified PBL obtained at the same time as biopsies. We didnot use the whole blood samples from Test Set 2 because high qualityprotein preparations cannot be obtained from PaxGene tubes. Differentialprotein expression was performed using a relative quantificationstrategy based on normalized spectral counts [31]. We identified 206differentially expressed proteins (p<0.05) for Banff 0 vs. Banff 1 (mildCAN/IFTA). In addition, we identified 135 proteins unique to Banff 0 and167 proteins unique to Banff 1. Class comparisons for Banff 0 vs. Banff2,3 (moderate/severe CAN/IFTA) yielded 282 differentially expressedproteins (p<0.05) and 509 proteins unique to Banff 2,3. We found 95proteins differentially expressed in mild and moderate/severe CAN/IFTAas compared to Banff 0, representing candidate protein markers for anystage of CAN/IFTA. In parallel, 94 proteins were differentiallyexpressed only in mild CAN/IFTA and these were linked to cell death,cell signaling, and post-translational protein modifications. The 168proteins differentially expressed only in moderate/severe CAN/IFTA werelinked to cellular morphology, growth and proliferation and signalingvia ERK/MAPK, acute phase responses, IGF1 and PPARa/RXRa.

There were 135 proteins unique to mild CAN/IFTA and 322 proteins uniqueto moderate/severe CAN/IFTA. Both mild and moderate/severe CAN/IFTA hadimmune and inflammation related proteins (20 and 37, respectively) butmany of these proteins are not mapped to the same functional pathways(e.g. calcium signaling in mild CAN/IFTA and apoptosis, NK cell and PTENsignaling for moderate/severe CAN/IFTA). In other cases, such assignaling via T and B cell receptors, IL4 and JAK/STAT, the samecanonical pathways were found but different unique proteins wereidentified.

Using only the differentially expressed proteins, DLDA obtained a 64%mean correct classification of mild CAN/IFTA and an 83% correctclassification for moderate/severe CAN/IFTA. In contrast, the uniqueproteins identified only in the blood of patients with biopsy-documentedmild (n=135) or moderate/severe CAN/IFTA (n=322), represent candidatebiomarkers with a 100% class prediction value in this data set.

We compiled the matches between proteins identified by mass spectrometryand mRNA transcripts identified using microarrays. The premise is thatprotein/transcript matches are a form of candidate biomarker validationbased on two independent technologies. There were 11 matches for the 393consensus genes for mild CAN/IFTA, 32 matches for the 1066 genes formild CAN/IFTA in Test Set 1 and 40 matches for the 1429 genes for mildCAN/IFTA in Test Set 2. There were no matches for the 62 consensus genesfor moderate/severe CAN/IFTA but 9 matches in the 172 genes formoderate/severe CAN/IFTA in Test Set 1 and 9 matches in the 545 genesfor moderate/severe CAN/IFTA in Test Set 2. All protein/transcriptmatches are listed in Tables 2-6.

Discussion

The primary objective of this study (also reported as [40]) was thediscovery of biomarkers in the peripheral blood of kidney transplantpatients with biopsy-documented interstitial fibrosis and tubularatrophy (IF/TA) and no known cause, which we refer to here as ChronicAllograft Nephropathy (CAN/IFTA)[14]. To this end, we integrated theresults of two, independently collected sets of patient samples thatwere significantly different in multiple clinical elements. Thus, theselection of biomarker candidates was not significantly influenced bythe time of biopsy (ranging from 1 to 6 years post-transplant), thespecific immunosuppressive protocols (use of different calcineurininhibitors vs. sirolimus) or the technology used to purify the mRNAtranscripts (density gradient-separated cells vs. whole blood). Thisexperimental design was chosen for its advantages in defining aconsensus set of robust candidate biomarkers for CAN/IFTA suitable forclinical use.

Using more closely matched sets of patient samples, for example,patients only 2 years post-transplant or only one source of blood cellRNA such as the PaxGene tubes might have resulted in higher totalnumbers of differentially expressed candidate mRNA transcripts andproteins. However, classifications for CAN/IFTA based on the consensusmRNA candidates described here for these otherwise very heterogeneousclinical data sets are 80% for mild CAN/IFTA and 92% for moderate/severeCAN/IFTA. By contrast, the widely used prostate specific antigen (PSA)biomarker, tested in an equally heterogenous human population, wasoriginally introduced with a predictive value of 28-35%[34] becausethere was no other minimally invasive option for early detection ofprostate cancer at that time, which is true for CAN/IFTA today.

We obtain very reasonable predictive accuracy, sensitivity andspecificity with 150, 100 and 50 total genes per signature. There arenow several technology platforms perfectly suitable for point ofclinical service implementation that can measure 100 genes or more costeffectively and within hours. In clinical practice, the differentiallyexpressed genes and proteins can be used for serial, prospectivemeasurements of the signature at regular intervals for the life of thekidney transplant. The absence of a positive CAN/IFTA signature at anypoint in time will indicate adequate immunosuppression orover-immunosuppression. Careful reductions in immunosuppressive drugdoses can then be used with repeat monitoring of the signature toestablish the optimal drug combination and level for each patient toprevent CAN/IFTA and ensure the long term safety of the therapy.

Biomarker discovery has been reported using peripheral blood profilingfor acute rejection in heart transplantation[35,36]. Peripheral bloodstudies of kidney transplant patients with “operational tolerance”included 22 patients with biopsy-documented CAN/IFTA[37]. Two of thegenes (DPYD, IRS2) reported to distinguish “operational tolerance” areidentified in our consensus sets. Our earlier study of 42 kidneybiopsies showed that gene expression profiles of CAN/IFTA hadsignificant up-regulation of immune/inflammation, fibrosis and tissueremodeling genes[16]. However, only 5 genes from these CAN/IFTA biopsieswere identified in the current peripheral blood consensus sets. A studyof 11 CAN/IFTA biopsies identified 3 genes linked to immunity andfibrosis that were tested by quantitative PCR in urine and peripheralblood with good correlations in urine but none in peripheral blood[38].Therefore, gene biomarkers identified in peripheral blood are mostlydistinct from those identified in tissue.

Although practice of the invention is not dependent on an understandingof mechanism, we propose that the peripheral blood represents a fullyfunctional and distinct compartment of the immune system that activelyserves to traffic and modulate all the components of effector immunity.Although the tissue injury that causes the progression of CAN/IFTA isoccurring in the kidney, we believe that a significant determinant ofthe phenotype of the host immune response, either acceptance of thegraft or CAN/IFTA, is actually established and subsequently regulatedwithin the peripheral blood compartment, lymph nodes and spleen.

Urine based proteomics have been used to report biomarkers for acuterejection using SELDI-TOF mass spectroscopy[23,39] but to our knowledgethis is the first study to identify blood cell-based proteomic markersfor transplantation using tandem mass spectroscopy. We have identifiedseveral hundred proteins that are significantly differentially expressedin peripheral blood of patients with CAN/IFTA as a function of histologygrade, mild to moderate/severe. The group of uniquely identifiedproteins potentially represents the highest value biomarker candidatesgiving 100% accuracy in our tests. Integrating proteomics with geneexpression, we identified over 80 protein/transcript matches forCAN/IFTA providing candidate validation based on two independenttechnologies. However, genes in which differential expression is foundonly at the gene or protein level but not both also allow accurateanalyses.

Although the invention has been described with reference to thepresently preferred embodiments, it should be understood that variousmodifications can be made without departing from the invention. Unlessotherwise apparent from the context any step, element, embodiment,feature or aspect of the invention can be used with any other.

All publications (including GenBank Accession numbers,UniProtKB/Swiss-Prot accession numbers and the like), patents and patentapplications cited are herein incorporated by reference in theirentirety for all purposes to the same extent as if each individualpublication, patent and patent application was specifically andindividually indicated to be incorporated by reference in its entiretyfor all purposes. In the event of any variance in sequences associatedwith Genbank, Unigene, International Protein Index, Entrez,UniProtKB/Swiss-Prot accession numbers and the like, the applicationrefers to the sequences associated with the cited accession numbers asof Jul. 9, 2009.

REFERENCES

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TABLE 1 Clinical Characteristics of the Study Populations. Test Set 1vs. Test Set 1 Test Set 2 Test Set 2 Signifi- Signifi- Signifi- Banff 0Banff 1 Banff 2, 3 cance Banff 0 Banff 1 Banff 2, 3 cance cance Number18 15 9 NA 8 14 13 NA NS Recipient age 42.61 ± 12.8 48.47 ± 11.6 45.67 ±17.5 NS 56.88 ± 12.2 51.36 ± 12.6 49.08 ± 12.9 NS Banff0 = 0.01Recipient 38.9 20 44.4 NS 62.5 35.7 53.8 NS NS gender (% female)Recipient race 22.22 13.33 11.11 NS 0 14.3 7.7 NS NS African AmericanPre tx diabetes 16.7 26.7 22.2 NS 25 14.3 7.7 NS NS PRA >20% (%) 5.6 6.711.1 NS 12.5 7.1 15.4 NS NS HLA mismatch 3.06 ± 1.7 2.66 ± 1.6 2.67 ±2.2 NS 3.43 + 2.4 4.33 + 1.4 3.58 + 1.6 NS Banff1 = 0.008 Deceased donor55.6 73.3 77.8 NS 75 71.4 46.2 NS NS % re-transplant 0 0 0 — 0 14.3 15.4NS NS Donor age 32.39 ± 15.7 42.33 ± 11.8 37.11 ± 12.1 Banff0 vs. 31.25± 19.3 41.54 ± 17.7 44.62 ± 13.4 NS NS Banff1 p = 0.05 Donor gender 5053.3 33.3 NS 12.5 57 53.8 NS NS female Donor race 16.7 13.3 11.1 NS 07.1 7.7 NS NS African American Induction 100 100 100 NS 75 21.4 23.1Banff0 vs. Banff1 = Banff1 0.0001 p = 0.026; Banff2, 3 = Banff0 vs.0.0005 Banff2, 3 p = 0.032 Serum  1.32 ± 0.38  1.45 ± 0.51  1.84 ± 0.77NS 1.70 + 1.3 2.41 + 0.7 3.09 + 1.2 Banff0 vs. Banff1 = CreatinineBanff2, 3 0.0002 p = 0.025 Banff2, 3 = 0.007 Time to Biopsy  755 ± 101 710 ± 109  659 ± 133 NS  420 ± 309  1664 ± 1364  2398 ± 1120 Banff0 vs.Banff0 = Banff1 0.05 p = 0.005; Banff 1 = Banff0 vs. 0.02 Banff2, 3Banff2, 3 = p = 0.00002 0.0001 CNI 38.9 60 77.8 NS 100 100 84.6 NSBanff0 = 0.007 MMF 100 93.3 88.9 NS 75 78.6 76.9 NS NS Steroids 100 100100 NS 37.5 100 92.3 Banff0 vs. Banff1 = Banff1 0.0009 p = 0.0002;Banff0 vs. Banff2, 3 p = 0.0022 C4d+ staining* ND ND ND NA NA 2 3 NS NAND—Not Done NA—Not Applicable NS—Not Significant

TABLE A Differentially expressed consensus genes for mild CAN for bothTest Mild CAN = CAN Banff Class 1; No evidence of CAN = CAN Banff Class0 Probesets with positive fold changes are upregulated in mild CAN GeomGeom mean mean of of intensities intensities Parametric in class 1: inclass 2: Fold p-value Banff 0 Banff 1 Change Probe Set ID Gene SymbolGene Title 1 0.000002 27.9 19.3 −1.45 203796_s_at BCL7A B-cellCLL/lymphoma 7A 2 2.1E−06 11.6 16.7 1.44 233650_at CEP63 centrosomalprotein 63 kDa 3 3.2E−06 50.5 40.1 −1.26 1552892_at TNFRSF13C tumornecrosis factor receptor superfamily, member 13C 4 5.9E−06 19.2 33.61.75 1565597_at EST1 Homo sapiens, clone IMAGE: 4275461, mRNA 5 8.3E−0615.1 23.5 1.56 241752_at SLC8A1 solute carrier family 8 (sodium/calciumexchanger), member 1 6 1.25E−05 803.7 1050.5 1.31 213702_x_at ASAH1N-acylsphingosine amidohydrolase (acid ceramidase) 1 7 1.61E−05 224.8174.8 −1.29 223259_at ORMDL3 ORM1-like 3 (S. cerevisiae) 8 1.84E−05135.4 189.9 1.40 204054_at PTEN phosphatase and tensin homolog (mutatedin multiple advanced cancers 1) 9 1.86E−05 26 46 1.77 239012_at IBRDC2IBR domain containing 2 10 2.39E−05 1182 1724.7 1.46 200975_at PPT1Palmitoyl-protein thioesterase 1 (ceroid-lipofuscinosis, neuronal 1,infantile) 11 0.000024 174.3 363.5 2.09 206584_at LY96 Lymphocyteantigen 96 12 3.35E−05 9 7.6 −1.18 228044_at C13orf21 Chromosome 13 openreading frame 21 13 4.41E−05 250.1 327.6 1.31 225492_at EST2 — 144.53E−05 7828 10660.2 1.36 202917_s_at S100A8 S100 calcium bindingprotein A8 15 0.000047 374.1 724.5 1.94 223501_at TNFSF13B Tumornecrosis factor (ligand) superfamily, member 13b 16 4.75E−05 112.7 2041.81 222496_s_at FLJ20273 RNA-binding protein 17 5.11E−05 22.4 38.8 1.73224996_at EST3 CDNA FLI39064 fis, clone NT2RP7014583 18 5.13E−05 21.617.5 −1.23 244863_at EST4 Transcribed locus 19 0.000052 7.5 9 1.20238791_at ZNF100 Zinc finger protein 100 20 5.66E−05 85.2 123.8 1.45218177_at CHMP1B Chromatin modifying protein 1B 21 5.67E−05 203.3 336.41.65 226208_at ZSWIM6 Zinc finger, SWIM-type containing 6 22 7.26E−05180.8 237.2 1.31 203778_at MANBA Mannosidase, beta A, lysosomal 230.000089 86.6 123.4 1.42 238903_at LOC137886 Hypothetical proteinLOC137886 24 0.000094 19.7 14.5 −1.36 214308_s_at HGD Homogentisate1,2-dioxygenase (homogentisate oxidase) 25 0.000103 492.9 744.6 1.51211368_s_at CASP1 Caspase 1, apoptosis-related cysteine peptidase(interleukin 1, beta, convertase) 26 0.000103 132.8 184.8 1.39 227017_atERICH1 Glutamate-rich 1 27 0.000107 10.3 15.5 1.50 228624_at TMEM144Transmembrane protein 144 28 0.000108 128.7 170.2 1.32 232149_s_at NSMAFNeutral sphingomyelinase (N-SMase) activation associated factor 290.000112 26.4 35.2 1.33 243287_s_at OSTM1 Osteopetrosis associatedtransmembrane protein 1 30 0.000116 59.5 134.7 2.26 1552773_at CLEC4DC-type lectin domain family 4, member D 31 0.000121 2887.4 3972.4 1.38202902_s_at CTSS Cathepsin S 32 0.000125 142.4 229 1.61 211744_s_at CD58CD58 molecule 33 0.000133 35.6 26.9 −1.32 243507_s_at C20orf196Chromosome 20 open reading frame 196 34 0.000137 101.9 77.4 −1.32228832_at FLJ20021 Hypothetical LOC90024 35 0.000149 1057.6 1433.5 1.36202727_s_at IFNGR1 Interferon gamma receptor 1 36 0.000169 40.5 55.51.37 213952_s_at ALOX5 Arachidonate 5-lipoxygenase 37 0.000174 364.6288.1 −1.27 219045_at RHOF Ras homolog gene family, member F (infilopodia) 38 0.000175 666 974.1 1.46 212268_at SERPINB1 Serpinpeptidase inhibitor, clade B (ovalbumin), member 1 39 0.00018 80.3 119.41.49 203276_at LMNB1 Lamin B1 40 0.00019 347.2 814.1 2.34 219666_atMS4A6A Membrane-spanning 4-domains, subfamily A, member 6A 41 0.00020454.9 110.9 2.02 204860_s_at NAIP /// NLR family, apoptosis inhibitoryprotein /// neuronal NAIP1B apoptosis inhibitory protein (centromeric)42 0.000212 3812.4 4958.6 1.30 202388_at RGS2 Regulator of G-proteinsignaling 2, 24 kDa 43 0.000226 24.5 43.9 1.79 1553514_a_at VNN3 Vanin 344 0.000239 84.6 108.3 1.28 218364_at LRRFIP2 Leucine rich repeat (inFLII) interacting protein 2 45 0.000242 15.5 21.5 1.39 218888_s_at NETO2Neuropilin (NRP) and tolloid (TLL)-like 2 46 0.000258 64.6 87.8 1.36204108_at NFYA Nuclear transcription factor Y, alpha 47 0.000273 35.650.1 1.41 213935_at ABHD5 Abhydrolase domain containing 5 48 0.000278 5475.5 1.40 208883_at UBR5 Ubiquitin protein ligase E3 componentn-recognin 5 49 0.000282 334.9 425 1.27 222148_s_at RHOT1 Ras homologgene family, member T1 50 0.000284 564.8 712.6 1.26 227266_s_at FYB FYNbinding protein (FYB-120/130) 51 0.000287 75.4 138.6 1.84 204714_s_at F5Coagulation factor V (proaccelerin, labile factor) 52 0.000302 6.3 5.6−1.13 229777_at CLRN3 Clarin 3 53 0.000302 16.9 19.2 1.14 241073_at EST5Transcribed locus 54 0.000309 29.8 52.7 1.77 1558549_s_at VNN1 Vanin 155 0.000319 584.3 710 1.22 201007_at HADHB Hydroxyacyl-Coenzyme Adehydrogenase/2-ketoacyl- Coenzyme A thiolase/enoyl-Coenzyme A hydratase(trifunctional protein), beta subunit 56 0.000323 9 7.8 −1.15 241171_atEST6 Transcribed locus 57 0.000328 18.4 33.5 1.82 239759_at EST7Transcribed locus 58 0.000368 44.5 76.4 1.72 209684_at RIN2 Ras and Rabinteractor 2 59 0.000369 22.6 18.4 −1.23 240654_at EST8 Transcribedlocus 60 0.00037 356 693 1.95 217738_at PBEF1 Pre-B-cell colonyenhancing factor 1 61 0.000377 48.8 73.7 1.51 228540_at QKI Quakinghomolog, KH domain RNA binding (mouse) 62 0.000386 24.1 20 −1.21221261_x_at MAGED4 /// Melanoma antigen family D, 4B///melanoma antigenMAGED4B family D, 4 63 0.000393 8.3 9.9 1.19 1562458_at UBE2WUbiquitin-conjugating enzyme E2W (putative) 64 0.000399 28.9 40.2 1.39227403_at PIGX Phosphatidylinositol glycan anchor biosynthesis, class X65 0.000406 21.6 27.6 1.28 226827_at TMEM165 Transmembrane protein 16566 0.000418 61.4 54.1 −1.13 1568691_at EST9 CDNA clone IMAGE: 3613441 670.000444 31 51.9 1.67 230343_at EST10 Transcribed locus 68 0.000445 10.38.2 −1.26 212650_at EHBP1 EH domain binding protein 1 69 0.000448 168.6306.1 1.82 238066_at RBP7 Retinol binding protein 7, cellular 700.000451 69.6 97.7 1.40 213292_s_at SNX13 Sorting nexin 13 71 0.00046338.7 63.7 1.65 228362_s_at FAM26F Family with sequence similarity 26,member F 72 0.000477 30 23.6 −1.27 236139_at EST11 Transcribed locus 730.000486 15.4 20.2 1.31 220775_s_at UEVLD UEV and lactate/malatedehydrogenase domains 74 0.000493 55.2 46.9 −1.18 221189_s_at TARS2Threonyl-tRNA synthetase 2, mitochondrial (putative) 75 0.000497 24.5 20−1.23 210150_s_at LAMA5 Laminin, alpha 5 76 0.000509 49.3 41.2 −1.20211304_x_at KCNJ5 Potassium inwardly-rectifying channel, subfamily J,member 5 77 0.000524 5.4 4.7 −1.15 233609_at PTPRK Protein tyrosinephosphatase, receptor type, K 78 0.000538 12.2 17.6 1.44 202422_s_atACSL4 Acyl-CoA synthetase long-chain family member 4 79 0.000539 360.3442.2 1.23 225284_at DNAJC3 /// DnaJ (Hsp40) homolog, subfamily C,member LOC144871 3///hypothetical protein LOC144871 80 0.000549 10.4 8.7−1.20 204983_s_at GPC4 Glypican 4 81 0.000555 15.5 13.4 −1.16 231318_atC15orf51 Chromosome 15 open reading frame 51 82 0.000564 59.4 83.9 1.41208158_s_at OSBPL1A Oxysterol binding protein-like 1A 83 0.000571 9.28.1 −1.14 205542_at STEAP1 Six transmembrane epithelial antigen of theprostate 1 84 0.000573 186.9 235.8 1.26 218905_at INTS8 Integratorcomplex subunit 8 85 0.000588 100.3 177.5 1.77 212820_at DMXL2 Dmx-like2 86 0.000594 160.5 341.8 2.13 215049_x_at CD163 CD163 molecule 870.000595 20.8 34.4 1.65 206674_at FLT3 Fms-related tyrosine kinase 3 880.000595 52.3 40.2 −1.30 233487_s_at LRRC8A Leucine rich repeatcontaining 8 family, member A 89 0.000607 17.5 21.1 1.21 33197_at MYO7AMyosin VIIA 90 0.000642 26.5 23.5 −1.13 203793_x_at PCGF2 Polycomb groupring finger 2 91 0.000648 9.1 8.2 −1.11 1566935_at TYRO3P TYRO3P proteintyrosine kinase pseudogene 92 0.000663 10.8 15.2 1.41 203767_s_at STSSteroid sulfatase (microsomal), isozyme S 93 0.000668 303.5 421.8 1.39226136_at GLIPR1 GLI pathogenesis-related 1 (glioma) 94 0.00067 52.181.1 1.56 216252_x_at FAS Fas (TNF receptor superfamily, member 6) 950.000694 244.7 420.5 1.72 221724_s_at CLEC4A C-type lectin domain family4, member A 96 0.000696 11.6 13.1 1.13 230419_at FLJ37644 Hypotheticalgene supported by AK094963 97 0.000701 26.8 33.2 1.24 225778_at FUT1Fucosyltransferase ! (galactoside 2-alpha-L- fucosyltransferase, H bloodgroup) 98 0.000702 14.8 10.3 −1.44 216063_at HBBP1 Hemoglobin, betapseudogene 1 99 0.000745 6.9 6.2 −1.11 207516_at CHRNB4 Cholinergicreceptor, nicotinic, beta 4 100 0.000749 21.8 17.3 −1.26 216910_atXPNPEP2 X-prolyl aminopeptidase (aminopeptidase P) 2, membrane-bound 1010.00075 14.7 12.5 −1.18 1555655_at OR10A4 Olfactory receptor, family 10,subfamily A, member 4 102 0.000755 266.1 339 1.27 225606_at BCL2L11BCL2-like 11 (apoptosis facilitator) 103 0.000768 17 14.8 −1.15207967_at VPS45 Vacuolar protein sorting 45 homolog (S. cerevisiae) 1040.000775 253.9 336.8 1.33 219079_at CYB5R4 Cytochrome b5 reductase 4 1050.000803 94.6 134.1 1.42 222498_at AZI2 5-azacytidine induced 2 1060.00081 570.4 686.2 1.20 210817_s_at CALCOCO2 Calcium binding andcoiled-coil domain 2 107 0.00082 344.4 494.4 1.44 211404_s_at APLP2Amyloid beta (A4) precursor-like protein 2 108 0.000824 9.6 16.4 1.711562481_at EST12 — 109 0.000834 78.3 105.7 1.35 203693_s_at E2F3 E2Ftranscription factor 3 110 0.00084 23.2 33.6 1.45 205841_at JAK2 Januskinase 3 (a protein tyrosine kinase) 111 0.000847 10.2 9.1 −1.121553504_at MRGPRX4 MAS-related GPR, member X4 112 0.00085 140.6 212.91.51 203139_at DAPK1 Death-associated protein kinase 1 113 0.000864186.1 235.2 1.26 226850_at SUMF1 Sulfatase modifying factor 1 1140.000896 4.9 5.4 1.10 230684_at GTPBP10 GTP-binding protein 10(putative) 115 0.000907 34.8 21.7 −1.60 228802_at RBPMS2 RNA bindingprotein with multiple splicing 2 116 0.000969 7.6 6.8 −1.12 204596_s_atSTC1 Stanniocalcin 1 117 0.000972 45.3 57 1.26 228061_at CCDC126Coiled-coil domain containing 126 118 0.000979 31.4 22.6 −1.39 244876_atEST13 — 119 0.000992 12.4 10.7 −1.16 233015_at MBNL1 Muscleblind-like(Drosophila) 120 0.001033 21.6 14.5 −1.49 234284_at GNG8 Guaninenucleotide binding protein (G protein), gamma 8 121 0.001036 38.2 24.8−1.54 1560262_at EST14 Homo sapiens, clone IMAGE: 5751523, mRNA 1220.001037 5.4 4.8 −1.13 1562902_at EST15 Homo sapiens, clone IMAGE:5176738, mRNA 123 0.001045 1215.1 2084.9 1.72 205863_at S100A12 S100calcium binding protein A12 124 0.001057 37.8 31.9 −1.18 222302_at EST16— 125 0.001065 44.9 51.1 1.14 212932_at RAB3GAP1 RAB3 GTPase activatingprotein subunit 1 (catalytic) 126 0.001066 36.3 49.6 1.37 233924_s_atEXOC6 Exocyst complex component 6 127 0.001087 34.5 41.5 1.20 230209_atEST17 CDNA FLI36477 fis, clone THYMU2017158 128 0.001103 498.4 419.3−1.19 41047_at C9orf16 Chromosome 9 open reading frame 16 129 0.00113657.1 40.8 −1.40 200884_at CKB Creatine kinase, brain 130 0.001137 177245.9 1.39 219157_at KLHL2 Kelch-like 2, Mayven (Drosophila) 1310.001153 7.3 6.4 −1.14 207818_s_at HTR7 5-hydroxytryptamine (serotonin)receptor 7 (adenylate cyclase-coupled) 132 0.001162 13.3 16.1 1.21234977_at ZADH2 Zinc binding alcohol dehydrogenase, domain containing 2133 0.001164 4.6 4.3 −1.07 238391_at EST18 Transcribed locus 1340.001173 125.2 160.3 1.28 222759_at SUV420H1 Suppressor of variegation4-20 homolog 1 (Drosophila) 135 0.001197 16.5 13.5 −1.22 233962_atC20orf120 Chromosome 20 open reading frame 120 136 0.001212 183 250.91.37 204526_s_at TBC1D8 TBC1 domain family, member 8 (with GRAM domain)137 0.001214 39.9 31.5 −1.27 235417_at SPOCD1 SPOC domain containing 1138 0.001228 67.2 87.8 1.31 1552472_a_at CENTB2 Centaurin, beta 2 1390.001232 423 513.3 1.21 200768_s_at MAT2A Methionine adenosyltransferaseII, alpha 140 0.001246 17 14.7 −1.16 229536_at REC8 REC8 homolog (yeast)141 0.001283 1790.8 2281.3 1.27 204220_at GMFG Glia maturation factor,gamma 142 0.001291 41.6 35.4 −1.18 234958_at EST19 Clone HQ0352 PRO0352143 0.001294 1519.9 1803 1.19 207168_s_at H2AFY H2A histone family,member Y 144 0.001329 9.9 8.3 −1.19 1557235_at EST20 CDNA FLI44051 fis,clone TESTI4033433 145 0.001329 7.7 6.8 −1.13 207120_at ZNF667 Zincfinger protein 667 146 0.001348 12 15.3 1.28 226688_at C3orf23Chromosome 3 open reading frame 23 147 0.001363 201.6 311.2 1.54224374_s_at EMILIN2 Elastin microfibril interfacer 2 148 0.001364 79.448.9 −1.62 244523_at MMD Monocyte to macrophagedifferentiation-associated 149 0.001415 10.4 9.1 −1.14 226533_at HINT3Histidine triad nucleotide binding protein 3 150 0.001421 505.7 358.5−1.41 202074_s_at OPTN Optineurin 151 0.001438 10.9 9.6 −1.14 234372_atLOC644728 Similar to Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)(38 kDa 8FA-dependent ADP- ribosylation substrate) (BARS-38) 1520.001448 239.8 331.7 1.38 202192_s_at GAS7 Growth arrest-specific 7 1530.001464 16.6 20.7 1.25 1559052_s_at PAK2 p21 (CDKN1A)-activated kinase2 154 0.001472 32.5 47.6 1.46 223304_at SLC37A3 Solute carrier family 37(glycerol-3-phosphate transporter), member 3 155 0.001491 43.1 58.5 1.36213582_at ATP11A ATPase, Class VI, type 11A 156 0.001507 6.5 5.8 −1.12233770_at EST21 CDNA FLI12077 fis, clone HEMBB1002453 157 0.001515 14.112.7 −1.11 234627_at FLJ21408 Hypothetical gene supported by AK025061158 0.00152 815.3 1047.6 1.28 209007_s_at C1orf63 Chromosome 1 openreading frame 63 159 0.00153 15.6 11.2 −1.39 214502_at HIST1H2BJ Histonecluster 1, H2bj 160 0.001533 206.6 140.7 −1.47 202124_s_at TRAK2Trafficking protein, kinesin binding 2 161 0.001538 16.1 12.9 −1.25223709_s_at WNT10A Wingless-type MMTV integration site family, member10A 162 0.001544 143.1 194.3 1.36 219132_at PELI2 Pellino homolog 2(Drosophila) 163 0.001561 556.9 684.6 1.23 217492_s_at LOC731292Phosphatase and tensin homolog (mutated in multiple /// PTEN ///advanced cancers 1) ///phosphatase and tensin PTENP1 homolog (mutated inmultiple advanced cancers 1), pseudogene 1///similar toPhosphatidylinositol-3,4,5- trisphosphate 3-phosphatase anddual-specificity protein phosphatase PTEN (Phosphatase and tensinhomolog) (Mutated in multiple advanced cancers1) 164 0.001562 7.4 6.7−1.10 241226_at EST22 Transcribed locus 165 0.001565 12.1 10.6 −1.14231965_at FAM113A Family with sequence similarity 113, member A 1660.00157 39.4 69.3 1.76 207605_x_at ZNF117 Zinc finger protein 117 1670.001602 22.4 19.4 −1.15 232249_at FMNL3 Formin-like 3 168 0.001612 81.2116 1.43 205698_s_at MAP2K6 Mitogen-activated protein kinase kinase 6169 0.001613 110.4 140.3 1.27 229798_s_at EST23 — 170 0.00162 21 17.7−1.19 219554_at RHCG Rh family, C glycoprotein 171 0.001625 7 6.1 −1.15244690_at EST24 Transcribed locus 172 0.00163 343.7 497.4 1.45225919_s_at C9orf72 Chromosome 9 open reading frame 72 173 0.001642 74.3101.7 1.37 213792_s_at INSR Insulin receptor 174 0.001677 23.1 26.8 1.16208328_s_at MEF2A Myocyte enhancer factor 2A 175 0.00168 6.9 6.2 −1.11207362_at SLC30A4 Solute carrier family 30 (zinc transporter), member 4176 0.001709 17.5 15.4 −1.14 206521_s_at GTF2A1 General transcriptionfactor IIA, 1, 19/37 kDa 177 0.001735 100.2 142 1.42 218027_at MRPL15Mitochondrial ribosomal protein L15 178 0.001737 19.6 22.8 1.16224198_at ELA1 Elastase 1, pancreatic 179 0.001741 69.6 97.1 1.40212572_at STK38L Serine/threonine kinase 38 like 180 0.001743 22.3 18.6−1.20 206993_at ATP5S ATP synthase, H+ transporting, mitochondrial F0complex, subunit s (factor B) 181 0.001788 45.4 36.5 −1.24 203479_s_atOTUD4 OTU domain containing 4 182 0.001835 13.4 11 −1.22 232820_s_atFAM112A Family with sequence similarity 112, member A 183 0.001854 7.26.6 −1.09 1558621_at CABLES1 Cdk5 and Abl enzyme substrate 1 1840.001854 59.1 49.6 −1.19 220765_s_at LIMS2 LIM and senescent cellantigen-like domains 2 185 0.001859 24.3 20.6 −1.18 205477_s_at AMBPAlpha-1-microglobulin/bikunin precursor 186 0.00189 102.8 59 0.57207826_s_at ID3 Inhibitor of DNA binding 3, dominant negative helix-loop-helix protein 187 0.001892 10.5 17.8 1.70 209992_at PFKFB26-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 188 0.001928 207.8151.9 −1.37 201841_s_at HSPB1 Heat shock 27 kDa protein 1 189 0.00193661.4 83.5 1.36 210768_x_at TMCO1 Transmembrane and coiled-coil domains 1190 0.001951 43.1 63.6 1.48 242794_at MAML3 Mastermind-like 3(Drosophila) 191 0.001976 58.7 79.2 1.35 213379_at COQ2 Coenzyme Q2homolog, prenyltransferase (yeast) 192 0.001983 425.9 650.8 1.53202446_s_at PLSCR1 Phospholipid scramblase 1 193 0.001984 24.7 28.7 1.16204210_s_at PCYT1A Phosphate cytidylyltransferase 1, choline, alpha 1940.001993 31.8 58.3 1.83 236898_at EST25 Transcribed locus. stronglysimilar to XP_0011011634.1 similar to tripartite motif-containing 25(Macaca mulatta) 195 0.002 8.8 7.4 −1.19 242661_x_at ALS2CR12Amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate12 196 0.002013 19.4 15.4 −1.26 1558773_s_at RANBP10 RAN binding protein10 197 0.002032 63.6 79.5 1.25 218896_s_at C17orf85 Chromosome 17 openreading frame 85 198 0.002033 27.8 37.2 1.34 220865_s_at PDSS1 Prenyl(decaprenyl) diphosphate synthase, subunit 1 199 0.002038 214.1 282.41.32 224511_s_at TXNDC17 Thioredoxin domain containing 17 200 0.0020457.6 6.4 −1.19 243347_at EST26 — 201 0.002054 8.1 7 −1.16 236336_at EST27CDNA clone IMAGE: 4796690 202 0.002098 153.9 205.6 1.34 224983_at SCARB2Scavenger receptor class B, member 2 203 0.002099 30.1 26 −1.161569144_a_at LOC653325 Similar to RIKEN cDNA 2310002J15 ///gene///hypothetical LOC653325 MGC59937 204 0.002104 15.9 13.7 −1.16234511_at C20orf86 Chromosome 20 open reading frame 86 205 0.002106 20.317.2 −1.18 237254_at SLC5A11 Solute carrier family 5 (sodium/glucosecotransporter), member 11 206 0.002112 9.3 10.5 1.13 231310_at EST28Transcribed locus 207 0.002171 15.7 13 −1.21 244226_s_at EST29 — 2080.0022 13.3 11.4 −1.17 230957_at PCDHB19P Protocadherin beta 19pseudogene 209 0.002206 10.8 9.5 −1.14 232321_at MUC17 Mucin 17, cellsurface associated 210 0.00221 27.4 19.8 −1.38 235557_at LOC150763Hypothetical protein LOC150763 211 0.002218 11251.4 8508.5 −1.32214414_x_at HBA2 Hemoglobin, alpha 2 212 0.00222 16.1 13.8 −1.171558118_at DGCR5 DiGeorge syndrome critical region gene 5 (non-coding)213 0.002223 18.1 15.9 −1.14 231994_at CHDH Choline dehydrogenase 2140.002229 29.1 34.7 1.19 212710_at CAMSAP1 Calmodulin regulatedspectrin-associated protein 1 215 0.002253 94.3 73.7 −1.28 243579_atMSI2 Musashi homolog 2 (Drosophila) 216 0.002256 446.2 305.3 −1.46200702_s_at DDX24 DEAD (Asp-Glu-Ala-Asp) box polypeptide 24 217 0.00226694.9 124.4 1.31 227046_at SLC39A11 Solute carrier family 39 (Metal iontransporter), member 11 218 0.002294 36 31.2 −1.15 40020_at CELSR3Cadherin, EGF LAG seven-pass G-type receptor 3 (flamingo homolog,Drosophila) 219 0.002303 27.6 22.9 −1.21 218903_s_at OBFC2BOligonucleotide/oligosaccharide-binding fold containing 2B 220 0.0023295.5 6.7 1.22 223861_at HORMAD1 HORMA domain containing 1 221 0.002348508.5 692.2 1.36 201926_s_at CD55 CD55 molecule, decay acceleratingfactor for complement (Cromer blood group) 222 0.00235 1265.9 1098.5−1.15 209075_s_at ISCU Iron-sulfur cluster scaffold homolog (E. coli)223 0.002351 7.1 6 −1.18 231721_at JAM3 Junctional adhesion molecule 3224 0.002354 8.2 7.4 −1.11 237505_at EST30 Transcribed locus 2250.002368 67.4 100.4 1.49 201952_at ALCAM Activated leukocyte celladhesion molecule 226 0.002389 10 8.7 −1.15 211896_s_at DCN Decorin 2270.002394 40.2 31.8 −1.26 216080_s_at FADS3 Fatty acid desaturase 3 2280.002427 252.5 326.4 1.29 202277_at SPTLC1 Serine palmitoyltransferase,long chain base subunit 1 229 0.002435 37.7 56.3 1.49 208488_s_at CR1Complement component (3b/4b) receptor 1 (Knops blood group) 230 0.002437100.3 135.1 1.35 213868_s_at DHRS7 Deydrogenase/reductase (SDR family)member 7 231 0.002443 314.9 419.1 1.33 225921_at NIN Ninein (GSK3Binteracting protein) 232 0.002447 56.7 82.8 1.46 233329_s_at KRCC1Lysine-rich coiled-coil 1 233 0.002472 28.3 24.6 −1.15 232663_s_atLOC390595 Similar to ubiquitin-associated protein 1 (predicted) 2340.002474 88.9 143.5 1.61 204150_at STAB1 Stabilin 1 235 0.002511 10 11.51.15 219831_at CDKL3 Cyclin-dependent kinase-like 3 236 0.002528 69.8101.9 1.46 216202_s_at SPTLC2 Serine palmitoyltransferase, long chainbase subunit 2 237 0.002536 28.7 24.3 −1.18 233381_at RUFY1 RUN and FYVEdomain containing 1 238 0.002552 67.7 84 1.24 222842_at EIF2C4Eukaryotic translation initiation factor 2C, 4 239 0.002566 13.7 10.6−1.29 1554413_s_at RUNDC2B /// RUN domain containing 2B///RUN domaincontaining RUNDC2C 2C 240 0.002598 13.9 12.2 −1.14 202403_s_at COL1A2Collagen, type 1, alpha 2 241 0.002603 531.4 440.6 −1.21 210950_s_atFDFT1 Farnesyl-diposphate farnesyltransferase 1 242 0.002605 10.1 8.5−1.19 215742_at EST31 CDNA FLI12157 fis, clone MAMMA1000500 243 0.00267235.9 42.2 1.18 221567_at NOL3 Nucleolar protein 3 (apoptosis repressorwith CARD domain) 244 0.002691 16 12 −1.33 203151_at MAP1AMicrotubule-associated protein 1A 245 0.002693 406.6 540.5 1.33208864_s_at TXN Thioredoxin 246 0.002706 83 62.3 −1.33 201072_s_atSMARCC1 SWI/SNF related, matrix associated, actin dependent regulator ofchromatin, subfamily c, member 1 247 0.002715 77.7 63.5 −1.22211358_s_at CIZ1 CDKN1A interacting zinc finger protein 1 248 0.00272411.1 13.7 1.23 205416_s_at ATXN3 Ataxin 3 249 0.002731 27 23.9 −1.13244694_at LOC402665 hCG1651476 250 0.002731 94.6 135.6 1.43 212511_atPICALM Phosphatidylinositol binding clathrin assembly protein 2510.002736 81.1 112.4 1.39 223978_s_at CRLS1 Cardiolipin synthase 1 2520.002737 12.1 10.7 −1.13 210923_at SLC1A7 Solute carrier family 1(glutamate transporter), member 7 253 0.002738 5.6 5.1 −1.10 204320_atCOL11A1 Collagen, type XI, alpha 1 254 0.002739 61 83.3 1.37 209666_s_atCHUK Conserved helix-loop-helix ubiquitous kinase 255 0.002747 29.9 24.5−1.22 238097_at EST32 — 256 0.002749 10.1 8.6 −1.17 205295_at CKMT2Creatine kinase, mitochondrial 2 (sarcomeric) 257 0.002773 240.1 331.41.38 1555797_a_at ARPC5 Actin related protein 2/3 complex, subunit 5, 16kDa 258 0.002776 32.5 28.1 −1.16 235402_at C11orf66 Chromosome 11 openreading frame 66 259 0.002793 30.8 25.5 −1.21 216562_at EST33 — 2600.002823 19.6 17.1 −1.15 1553967_at ADAT3 Adenosine deaminase,tRNA-specific 3, TAD3 homolog (S. cerevisiae) 261 0.002831 883.8 1069.31.21 226525_at EST34 Transcribed locus 262 0.002853 65.1 109.4 1.68220034_at IRAK3 Interleukin-1 receptor-associated kinase 3 263 0.0028567.7 7.1 −1.08 1563656_at EST35 MRNA; cDNA DKFZp586H1217 (from cloneDKFZp586H1217) 264 0.002859 60.5 53.8 −1.12 233235_x_at EST36 CDNA:FLI21443 fis, clone COL04430 265 0.002876 5 5.5 1.10 1558640_a_atLOC728411 Similar to Beta-glucuronidase precursor 266 0.00288 143.4216.8 1.51 204646_at DPYD Dihydropyrimidine dehydrogenase 267 0.00288852.8 83.6 1.58 207719_x_at CEP170 Centrosomal protein 170 kDa 2680.00289 41.3 50.9 1.23 228791_at C15orf38 Chromosome 15 open readingframe 38 269 0.002915 17.6 15 −1.17 240705_at CYP19A1 Cytochrome P450,family 19, subfamily A, polypeptide 1 270 0.002927 50.7 42.9 −1.18218725_at SLC25A22 Solute carrier family 25 (mitochondrialcarrier:glutamate), member 22 271 0.002996 105.1 163.4 1.55 201328_atETS2 v-ets erythroblastosis virus E26 oncogene homolog 2 (avian) 2720.002997 13.9 16.3 1.17 239332_at EST37 Homo sapiens, clone IMAGE:3897156, mRNA 273 0.00302 14 16.9 1.21 240394_at EST38 Transcribed locus274 0.003049 60.3 51.8 −1.16 1556900_at LOC149773 Hypothetical proteinLOC149773 275 0.003057 43.4 33.4 −1.30 220588_at BCAS4 Breast carcinomaamplified sequence 4 276 0.003067 10.1 8.4 −1.20 210127_at RAB6B RAB6B,member RAS oncogene family 277 0.003068 5.5 4.9 −1.12 1559450_at EST39CDNA clone IMAGE: 5286225 278 0.003109 22 36.6 1.66 1558920_at EST40CDNA FLI43417 fis, clone OCBBF2026025 279 0.003116 9.2 8.2 −1.12206847_s_at HOXA7 Homeobox A7 280 0.003117 12.9 11.3 −1.14 216303_s_atMTMR1 Myotubularin related protein 1 281 0.003131 14 12.3 −1.14216799_at EST41 MRNA; cDNA DKFZp547G044 (from clone DKFZp547G044) 2820.003131 5.8 5.3 −1.09 242130_at EST42 Transcribed locus 283 0.00314510.6 9.4 −1.13 1562106_at EST43 Homo sapiens, clone IMAGE: 5240933, mRNA284 0.003147 40.2 46.9 1.17 224416_s_at MED28 Mediator complex subunit28 285 0.003153 441.7 716.5 1.62 203799_at CD302 CD302 molecule 2860.00318 23.2 19.5 −1.19 243062_at FLCN Folliculin 287 0.003188 15.1 19.71.30 239574_at EST44 Transcribed locus 288 0.003189 5.7 5.2 −1.101559518_at HSD17B12 Hydroxysteroid (17-beta) dehydrogenase 12 289 0.003227.3 38.8 1.42 207601_at SULT1B1 Sulfotransferase family, cytosolic, 1B,member 1 290 0.003219 14.6 13 −1.12 219576_at MAP7D3 MAP7 domaincontaining 3 291 0.003229 98.4 127.1 1.29 209234_at KIF1B Kinesin familymember 1B 292 0.003234 151.4 100.7 −1.50 225775_at TSPAN33 Tetraspanin33 293 0.003255 10.8 12.9 1.19 238921_at LOC641767 Hypothetical proteinLOC641767///hypothetical /// LOC644794 LOC644794 294 0.003276 5.2 5.81.12 236262_at MMRN2 Multimerin 2 295 0.003296 20.4 16.2 −1.26 215526_atEST45 MRNA; cDNA DKFZp586C2020 (from clone DKFZp586C2020) 296 0.00329614.9 13.2 −1.13 236914_at EST46 Transcribed locus, moderately similar toXP_001137307.1 hypothetical protein (Pan troglodytes) 297 0.003306 43.658.4 1.34 236465_at RNF175 Ring finger protein 175 298 0.00334 106.2210.1 1.98 204619_s_at VCAN Versican 299 0.003365 15.3 12.5 −1.22243365_s_at AUTS2 Autism susceptibility candidate 2 300 0.003378 165.7146 −1.13 201618_x_at GPAA1 Glycosylphosphatidylinositol anchorattachment protein 1 homolog (yeast) 301 0.003383 82.2 97.6 1.19209445_x_at C7orf44 Chromosome 7 open reading frame 44 302 0.003388 66.1101.4 1.53 1552485_at LACTB Lactamase, beta 303 0.003393 6 5.5 −1.091558010_s_at SLC1A2 Solute carrier family 1 (glial high affinityglutamate transporter), member 2 304 0.003404 8 11 1.38 225008_at EST47CDNA FLI39064 fis, clone NT2RP7014583 305 0.003412 13.5 11.3 −1.191560108_at EST48 CDNA FLI30757 fis, clone FEBRA2000468 306 0.003423 29.327.2 −1.08 244055_at EST49 Transcribed locus 307 0.003447 16.6 20 1.20233750_s_at C1orf25 Chromosome 1 open reading frame 25 308 0.00346 5.4 5−1.08 220361_at IQCH IQ motif containing H 309 0.003472 110 181.2 1.65222303_at EST50 — 310 0.003502 58.3 80.3 1.38 230937_at LOC285835Hypothetical protein LOC285835 311 0.003535 39.4 52 1.32 207627_s_atTFCP2 Transcription factor CP2 312 0.003539 20.3 17.5 −1.16 1555752_atSTH Saitohin 313 0.003542 3088.2 3805.3 1.23 212501_at CEBPBCCAAT/enhancer binding protein (C/EBP), beta 314 0.003551 6.2 5.7 −1.09244675_at RGS8 Regulator of G-protein signaling 8 315 0.003571 12.7 11.2−1.13 208275_x_at UTF1 Undifferentiated embryonic cell transcriptionfactor 1 316 0.003572 397.4 524.7 1.32 210951_x_at RAB27A RAB27A, memberRAS oncogene family 317 0.003582 7.8 6.7 −1.16 219840_s_at TCL6 T-cellleukemia/lymphoma 6 318 0.003626 124.1 166.3 1.34 219256_s_at SH3TC1 SH3domain and tetratricopeptide repeats 1 319 0.003657 5.3 4.8 −1.101558778_s_at MKL2 MKL/myocardin-like 2 320 0.00366 32.1 27.1 −1.18218480_at AGBL5 ATP/GTP binding protein-like 5 321 0.003672 118 176.71.50 204099_at SMARCD3 SWI/SNF related, matrix associated, actindependent regulator of chromatin, subfamily d, member 3 322 0.003678480.1 579 1.21 225750_at EST51 CDNA FLI14162 fis, clone NT2RM4002504 3230.003715 50.7 43.5 −1.17 214253_s_at DTNB Dystrobrevin, beta 3240.003718 12.1 10.8 −1.12 243048_at CECR7 Cat eye syndrome chromosomeregion, candidate 7 325 0.003757 9 7.9 −1.14 1556012_at KLHDC7A Kelchdomain containing 7A 326 0.003773 17.6 23.4 1.33 215285_s_at PHTF1Putative homeodomain transcription factor 1 327 0.00378 64.4 81.7 1.27231321_s_at PHCA Phytoceramidase, alkaline 328 0.003783 5.4 4.9 −1.10238901_at EST52 Full length insert cDNA clone ZE01A04 329 0.003793 25.421.4 −1.19 214595_at KCNG1 Potassium voltage-gated channel, subfamily G,member 1 330 0.0038 10.5 9.4 −1.12 216470_x_at PRSS1 /// Protease,serine, 1 (trypsin1)///protease, serine, 2 PRSS2 ///(trypsin2)///protease, serine, 3 (mesotrypsin) PRSS3 /// trypsinogen 3TRY6 331 0.003819 36.6 59.4 1.62 204787_at VSIG4 V-set andimmunoglobulin domain containing 4 332 0.003841 11.7 10.2 −1.15216101_at EST53 Full length insert cDNA clone YR67C11 333 0.003845 5175.1 1.47 224862_at GNAQ Guanine nucleotide binding protein (G protein),q polypeptide 334 0.003873 17.6 23.6 1.34 234664_at LOC284701Hypothetical protein LOC284701 335 0.003878 16.8 14 −1.20 202796_atSYNPO Synaptopodin 336 0.003884 11.4 10 −1.14 238217_at EST54Transcribed locus 337 0.003905 559.2 823.8 1.47 209184_s_at IRS2 Insulinreceptor substrate 2 338 0.003905 5.6 5.2 −1.08 1565578_at EST55 CDNAFLI34486 fis, clone HLUNG2004217 339 0.003909 202.6 269.2 1.33217823_s_at UBE2J1 Ubiquitin-conjugating enzyme E2, J1 (UBC6 homolog,yeast) 340 0.003952 7 6.2 −1.13 240873_x_at DAB2 Disabled homolog 2,mitogen-responsive phosphoprotein (Drosophila) 341 0.003967 206.9 281.11.36 212795_at KIAA1033 KIAA1033 342 0.003968 36 48.9 1.36 239085_atEST56 Transcribed locus 343 0.003972 110.8 171.2 1.55 223423_at GPR160 Gprotein-coupled receptor 160 344 0.003992 12.3 10.8 −1.14 238917_s_atMGC24039 Hypothetical protein MGC24039 345 0.003999 36.9 48.4 1.31226395_at LOC286170 Hypothetical protein LOC286170 346 0.004021 155.6222.8 1.43 215000_s_at FEZ2 Fasciculation and elongation protein zeta 2(zygin II) 347 0.004032 196.3 235.6 1.20 203605_at SRP54 Signalrecognition particle 54 kDa 348 0.004054 7.7 6.6 −1.17 242805_at EST57 —349 0.004085 50.4 66.2 1.31 204043_at TCN2 Transcobalamin II; macrocyticanemia 350 0.004142 9.8 11.4 1.16 237845_at EST58 Transcribed locus,moderately similar to XP_001103240.1 similar to kinesin family member 27(Macaca mulatta) 351 0.004144 28.5 22.5 −1.27 1569499_at EST59 CDNAclone IMAGE: 3840913 352 0.004179 21.1 18.5 −1.14 217876_at GTF3C5General transcription factor IIIC, polypeptide 5, 63 kDa 353 0.0041859.9 15.3 1.55 223660_at ADORA3 Adenosine A3 receptor 354 0.004186 5.86.3 1.09 231160_at EST60 Transcribed locus 355 0.00419 9.7 15.7 1.62236901_at EST61 Transcribed locus 356 0.0042 20.9 18 −1.16 215979_s_atSLC7A1 Solute carrier family 7 (cationic amino acid transporter, y+system), member 1 357 0.004234 1525.2 1779.3 1.17 208736_at ARPC3 Actinrelated protein 2/3 complex, subunit 3, 21 kDa 358 0.004238 82.6 123.21.49 229383_at EST62 CDNA FLI34016 fis, clone FCBBF2002541 359 0.00426532 27.2 −1.18 32137_at JAG2 Jagged 2 360 0.004278 7.6 6.9 −1.10213249_at FBXL7 F-box and leucine-rich repeat protein 7 361 0.0042882770.3 3252 1.17 202803_s_at ITGB2 Integrin, beta 2 (complementcomponent 3 receptor 3 and 4 subunit) 362 0.004321 119 159.5 1.34203310_at STXBP3 Syntaxin binding protein 3 363 0.004335 798.5 1181 1.48202295_s_at CTSH Cathespin H 364 0.004354 10.4 9.1 −1.14 220994_s_atSTXBP6 Syntaxin binding protein 6 (amisyn) 365 0.004355 49 90.4 1.84212224_at ALDH1A1 Aldehyde dehydrogenase 1 family, member A1 3660.004381 208.3 260.9 1.25 212120_at RHOQ Ras homolog gene family, memberQ 367 0.004435 32.8 29.9 −1.10 37586_at ZNF142 Zinc finger protein 142368 0.004453 285.1 404.8 1.42 219356_s_at CHMP5 Chromatin modifyingprotein 5 369 0.004458 118.6 152.6 1.29 241370_at LOC286052 Hypotheticalprotein LOC286052 370 0.004465 13.1 11.4 −1.15 1558476_at C1orf165Chromosome 1 open reading frame 165 371 0.004485 5.5 6.2 1.13 206533_atCHRNA5 Cholinergic receptor, nicotinic, alpha 5 372 0.004489 33.2 28.8−1.15 229979_x_at EST63 Transcribed locus 373 0.004526 66.2 83.5 1.26200764_s_at CTNNA1 Catenin (cadherin-associated protein), alpha 1, 102kDa 374 0.004556 7.3 6.5 −1.12 240874_at EST64 Transcribed locus 3750.004558 20.4 17.2 −1.19 1556672_a_at RBM6 RNA binding motif protein 6376 0.004559 13.6 10.9 −1.25 236268_at SEC22C SEC22 vesicle traffickingprotein homolog C (S. cerevisiae) 377 0.004594 68.3 57 −1.20 220968_s_atTSPAN9 Tetraspanin 9 378 0.004616 363.3 284.7 −1.28 223042_s_at FUNDC2FUN14 domain containing 2 379 0.004683 6.9 9.4 1.36 226311_at EST65 CDNAclone IMAGE: 30924414 380 0.004699 5 4.7 −1.06 1570482_at EST66 Pp14356381 0.00476 5.9 6.6 1.12 1562274_at EST67 MRNA; cDNA DKFZp 313I0929(from clone DKFZp313I0929) 382 0.004769 40.5 32.8 −1.23 201792_at AEBP1AE binding protein 1 383 0.004776 11.7 13.7 1.17 229671_s_at C21orf45Chromosome 21 open reading frame 45 384 0.004783 23 15.8 −1.46 208501_atGFI1B Growth factor independent 1B (potential regulator of CDKN1A,translocated in CML) 385 0.004788 6.6 5.9 −1.12 206142_at ZNF135 Zingfinger protein 135 386 0.004813 6.9 6.4 −1.08 233594_at EST68 CDNA cloneIMAGE: 4823221 387 0.004845 9 8 −1.13 1565407_at LHX9 LIM homeobox 9 3880.004861 7.1 6.3 −1.13 1559634_at CHRM3 Cholinergic receptor, muscarinic3 389 0.004927 23.8 36.5 1.53 236297_at EST69 CDNA FLI45742 fis, cloneKIDNE2016327 390 0.004932 29.6 33.1 1.12 215930_s_at CTAGE5 CTAGEfamily, member 5 391 0.004946 101.1 128.9 1.27 209463_s_at TAF12 TAF12RNA polymerase II, TATA box binding protein (TBP)-associated factor, 20kDa 392 0.004975 26.4 18.6 −1.42 206759_at FCER2 Fc fragment of IgE, lowaffinity II, receptor for (CD23) 393 0.004988 14.3 12.3 −1.16 230950_atEST70 Transcribed locus

TABLE B Differentially expressed consensus genes for moderate/severeCAN/IFTA for both Test Sets Moderate/Severe CAN/IFTA = CAN/IFTA BanffClass 2, 3; No evidence of CAN/IFTA = CAN/IFTA Banff Class 0 Probesetswith positive fold changes are upregulated in moderate/severe CAN GeomGeom mean of mean of intensities intensities Ratio of Parametric inclass 1: in class 2: geom p-value Banff 0 Banff 2, 3 means Probe Set IDGene Symbol Gene Title 1 0.0001775 11.1 9 −1.23 1566879_at EST1 ATP/GTPbinding protein-like 1 2 0.0003852 4.9 4.5 −1.09 241139_at EST2 — 30.0004281 5.5 6.1 1.11 231591_at BHMT anthrax toxin receptor 2 40.0004852 20.5 26.2 1.28 242619_x_at EST3 — 5 0.0005716 20.8 34.5 1.66206674_at FLT3 LIM homeobox 9 6 0.0005983 5.6 4.9 −1.14 204005_s_at PAWR— 7 0.0006361 23 39.6 1.72 220112_at ANKRD55 — 8 0.0006841 6.6 5.9 −1.12239312_at EST4 Phospholipase C epsilon 9 0.0007962 21.4 28.1 1.31205977_s_at EPHA1 — 10 0.0008868 9.3 8.1 −1.15 210412_at GRIN2Bolfactory receptor, family 8, subfamily G, member 1 11 0.0008881 5 4.5−1.11 216089_at MCFD2L — 12 0.0009531 10 8.5 −1.18 226211_at MEG3 PRKC,apoptosis, WT1, regulator 13 0.001086 58.7 72.7 1.24 226856_at MUSTN1CUG triplet repeat, RNA binding protein 1 14 0.001156 11.7 14.7 1.26229671_s_at C21orf45 PBX/knotted 1 homeobox 1 15 0.001212 10 11.6 1.16219831_at CDKL3 cleavage stimulation factor, 3′ pre-RNA, subunit 2, 64kDa 16 0.0013123 8.7 10 1.15 233429_at FLJ23577 matrix metallopeptidase1 (interstitial collagenase) 17 0.0013489 14 19 1.36 210896_s_at ASPHIKAROS family zinc finger 1 (Ikaros) 18 0.0014846 9.7 15 1.55 236901_atEST5 EPH receptor A1 19 0.0015437 7.7 6.8 −1.13 213994_s_at SPON1fms-related tyrosine kinase 3 20 0.0015498 11 9.5 −1.16 242417_atLOC283278 cytochrome P450, family 4, subfamily B, polypeptide 1 210.0015652 6.3 5.6 −1.13 229777_at CLRN3 glutamate receptor, ionotropic,N-methyl D-aspartate 2B 22 0.0016885 311.3 218.7 −1.42 205039_s_at IKZF1aspartate beta-hydroxylase 23 0.0017597 18.8 22.5 1.20 204113_at CUGBP1nuclear factor of kappa light polypeptide gene enhancer in B-cells 2(p49/p100) 24 0.0019344 11.6 14.8 1.28 233650_at CEP63 metproto-oncogene (hepatocyte growth factor receptor) 25 0.0019513 42.8 571.33 236832_at LOC221442 spondin 1, extracellular matrix protein 260.0019757 21.9 18.6 −1.18 228721_at C3orf41 — 27 0.0020356 6.9 8.9 1.29226311_at EST6 secretogranin III 28 0.0020555 5.5 4.6 −1.20 1566428_atEST7 cyclin-dependent kinase-like 3 29 0.0020848 18.7 15 −1.25 229532_atZNF502 ankyrin repeat domain 55 30 0.0021794 10.6 12 1.13 1554615_atEST8 heparan-alpha-glucosaminide N-acetyltransferase 31 0.0022636 5.95.4 −1.09 230650_at EST9 family with sequence similarity 135, member A32 0.0022797 76.1 62.4 −1.22 204459_at CSTF2 maternally expressed 3(non-protein coding) 33 0.0023808 5.3 4.8 −1.10 1570050_at EST10 — 340.0023855 4.7 4.3 −1.09 1566096_x_at EST11 musculoskeletal, embryonicnuclear protein 1 35 0.0025531 9 8 −1.13 1565407_at LHX9 hexokinasedomain containing 1 36 0.0025848 5.1 5.6 1.10 232770_at TUSC3 — 370.0026131 6.4 5.6 −1.14 204475_at MMP1 hypothetical protein LOC90784 380.0026527 11.3 14.3 1.27 243349_at KIAA1324 thyroid hormone receptor,beta (erythroblastic leukemia viral (v-erb-a) oncogene homolog 2, avian)39 0.0027257 5.7 5.1 −1.12 240604_at EXOD1 chromosome 3 open readingframe 41 40 0.0027342 6 5.6 −1.07 210096_at CYP4B1 RNA binding proteinwith multiple splicing 2 41 0.0027896 39.3 22 −1.79 228390_at EST12hypothetical protein LOC729680 42 0.0027907 6.3 6.9 1.10 228977_atLOC729680 nuclear receptor subfamily 2, group F, member 2 43 0.00282159.5 10.6 1.12 213807_x_at MET zinc finger protein 502 44 0.0028343 7.96.7 −1.18 228716_at THRB CDNA FU90800 fis, clone Y79AA1000127 450.0029105 6.1 10.7 1.75 1560800_at EST13 clarin 3 46 0.0031196 12.6 14.31.13 1567060_at OR8G1 — 47 0.0033408 24.1 19.6 −1.23 223497_at FAM135ABetaine:homocysteine methyltransferase 48 0.0039416 5.3 5.9 1.11211524_at NFKB2 tumor suppressor candidate 3 49 0.0039539 14.2 12.3−1.15 241261_x_at EST14 sperm flagellar 2 50 0.003958 12.1 10.5 −1.15243048_at CECR7 centrosomal protein 63 kDa 51 0.0040206 34.8 22.1 −1.57228802_at RBPMS2 — 52 0.004032 4.7 4.4 −1.07 219196_at SCG3 hypotheticalLOC221442 53 0.0041033 18.9 24.7 1.31 227614_at HKDC1 — 54 0.004179939.2 46 1.17 204195_s_at PKNOX1 — 55 0.0042431 25 30.2 1.21 228515_atLOC90784 exoribonuclease 2 56 0.0042468 9.7 8.7 −1.11 1566739_at PLCE1 —57 0.0043315 27.7 33.5 1.21 222491_at HGSNAT — 58 0.0044839 7.3 8.1 1.111553447_at AGBL1 — 59 0.0045669 6.7 6.2 −1.08 229092_at EST15hypothetical protein LOC283278 60 0.0047554 9.7 11.1 1.14 233993_atEST16 — 61 0.004775 17.7 21 1.19 242264_at EST17 cat eye syndromechromosome region, candidate 7 62 0.0048752 34.1 38.1 1.12 1555536_atANTXR2 KIAA1324

TABLE C Differentially expressed consensus genes for mild CAN/IFTA forboth Test Sets Mild CAN/IFTA = CAN/IFTA Banff Class 1; No evidence ofCAN/IFTA = CAN/IFTA Banff Class 0 Probesets with positive fold changesare upregulated in mild CAN Geom Geom mean of mean of intensitiesintensities Parametric in class 1: in class 2: Fold p-value Banff 0Banff 1 Change Probe Set ID Gene Symbol Gene Title 1 0.000002 27.9 19.3−1.45 203796_s_at BCL7A B-cell CLL/lymphoma 7A 2 2.1E−06 11.6 16.7 1.44233650_at CEP63 centrosomal protein 63 kDa 3 3.2E−06 50.5 40.1 −1.261552892_at TNFRSF13C tumor necrosis factor receptor superfamily, member13C 4 5.9E−06 19.2 33.6 1.75 1565597_at EST1 Homo sapiens, clone IMAGE:4275461, mRNA 5 8.3E−06 15.1 23.5 1.56 241752_at SLC8A1 solute carrierfamily 8 (sodium/calcium exchanger), member 1 6 1.25E−05 803.7 1050.51.31 213702_x_at ASAH1 N-acylsphingosine amidohydrolase (acidceramidase) 1 7 1.61E−05 224.8 174.8 −1.29 223259_at ORMDL3 ORM1-like 3(S. cerevisiae) 8 1.84E−05 135.4 189.9 1.40 204054_at PTEN phosphataseand tensin homolog (mutated in multiple advanced cancers 1) 9 1.86E−0526 46 1.77 239012_at IBRDC2 IBR domain containing 2 10 2.39E−05 11821724.7 1.46 200975_at PPT1 palmitoyl-protein thioesterase 1(ceroid-lipofuscinosis, neuronal 1, infantile) 11 0.000024 174.3 363.52.09 206584_at LY96 lymphocyte antigen 96 12 3.35E−05 9 7.6 −1.18228044_at C13orf21 chromosome 13 open reading frame 21 13 4.41E−05 250.1327.6 1.31 225492_at EST2 — 14 4.53E−05 7828 10660.2 1.36 202917_s_atS100A8 S100 calcium binding protein A8 15 0.000047 374.1 724.5 1.94223501_at TNFSF13B tumor necrosis factor (ligand) superfamily, member13b 16 4.75E−05 112.7 204 1.81 222496_s_at FLJ20273 RNA-binding protein17 5.11E−05 22.4 38.8 1.73 224996_at EST3 CDNA FLJ39064 fis, cloneNT2RP7014583 18 5.13E−05 21.6 17.5 −1.23 244863_at EST4 Transcribedlocus 19 0.000052 7.5 9 1.20 238791_at ZNF100 zinc finger protein 100 205.66E−05 85.2 123.8 1.45 218177_at CHMP1B chromatin modifying protein 1B21 5.67E−05 203.3 336.4 1.65 226208_at ZSWIM6 zinc finger, SWIM-typecontaining 6 22 7.26E−05 180.8 237.2 1.31 203778_at MANBA mannosidase,beta A, lysosomal 23 0.000089 86.6 123.4 1.42 238903_at LOC137886hypothetical protein LOC137886 24 0.000094 19.7 14.5 −1.36 214308_s_atHGD homogentisate 1,2-dioxygenase (homogentisate oxidase) 25 0.000103492.9 744.6 1.51 211368_s_at CASP1 caspase 1, apoptosis-related cysteinepeptidase (interleukin 1, beta, convertase) 26 0.000103 132.8 184.8 1.39227017_at ERICH1 glutamate-rich 1 27 0.000107 10.3 15.5 1.50 228624_atTMEM144 transmembrane protein 144 28 0.000108 128.7 170.2 1.32232149_s_at NSMAF neutral sphingomyelinase (N-SMase) activationassociated factor 29 0.000112 26.4 35.2 1.33 243287_s_at OSTM1osteopetrosis associated transmembrane protein 1 30 0.000116 59.5 134.72.26 1552773_at CLEC4D C-type lectin domain family 4, member D 310.000121 2887.4 3972.4 1.38 202902_s_at CTSS cathepsin S 32 0.000125142.4 229 1.61 211744_s_at CD58 CD58 molecule 33 0.000133 35.6 26.9−1.32 243507_s_at C20orf196 chromosome 20 open reading frame 196 340.000137 101.9 77.4 −1.32 228832_at FLJ20021 hypothetical LOC90024 350.000149 1057.6 1433.5 1.36 202727_s_at IFNGR1 interferon gamma receptor1 36 0.000169 40.5 55.5 1.37 213952_s_at ALOX5 Arachidonate5-lipoxygenase 37 0.000174 364.6 288.1 −1.27 219045_at RHOF ras homologgene family, member F (in filopodia) 38 0.000175 666 974.1 1.46212268_at SERPINB1 serpin peptidase inhibitor, clade B (ovalbumin),member 1 39 0.00018 80.3 119.4 1.49 203276_at LMNB1 lamin B1 40 0.00019347.2 814.1 2.34 219666_at MS4A6A membrane-spanning 4-domains, subfamilyA, member 6A 41 0.000204 54.9 110.9 2.02 204860_s_at NAIP /// NLRfamily, apoptosis inhibitory protein /// neuronal NAIP1B apoptosisinhibitory protein (centromeric) 42 0.000212 3812.4 4958.6 1.30202388_at RGS2 regulator of G-protein signaling 2, 24 kDa 43 0.00022624.5 43.9 1.79 1553514_a_at VNN3 vanin 3 44 0.000239 84.6 108.3 1.28218364_at LRRFIP2 leucine rich repeat (in FLII) interacting protein 2 450.000242 15.5 21.5 1.39 218888_s_at NETO2 neuropilin (NRP) and tolloid(TLL)-like 2 46 0.000258 64.6 87.8 1.36 204108_at NFYA nucleartranscription factor Y, alpha 47 0.000273 35.6 50.1 1.41 213935_at ABHD5abhydrolase domain containing 5 48 0.000278 54 75.5 1.40 208883_at UBR5ubiquitin protein ligase E3 component n-recognin 5 49 0.000282 334.9 4251.27 222148_s_at RHOT1 ras homolog gene family, member T1 50 0.000284564.8 712.6 1.26 227266_s_at FYB FYN binding protein (FYB-120/130)

TABLE D Top 50 Differentially expressed consensus genes formoderate/severe CAN/IFTA for both Test Sets Moderate/Severe CAN/IFTA =CAN/IFTA Banff Class 2, 3; No evidence of CAN/IFTA = CAN/IFTA BanffClass 0 Geom Geom mean of mean of intensities intensities Ratio ofParametric in class 1: in class 2: geom p-value Banff 0 Banff 2, 3 meansProbe Set ID Gene Symbol Gene Title 1 0.000178 11.1 9 −1.23 1566879_atEST1 ATP/GTP binding protein-like 1 2 0.000385 4.9 4.5 −1.09 241139_atEST2 — 3 0.000428 5.5 6.1 1.11 231591_at BHMT anthrax toxin receptor 2 40.000485 20.5 26.2 1.28 242619_x_at EST3 — 5 0.000572 20.8 34.5 1.66206674_at FLT3 LIM homeobox 9 6 0.000598 5.6 4.9 −1.14 204005_s_at PAWR— 7 0.000636 23 39.6 1.72 220112_at ANKRD55 — 8 0.000684 6.6 5.9 −1.12239312_at EST4 Phospholipase C epsilon 9 0.000796 21.4 28.1 1.31205977_s_at EPHA1 — 10 0.000887 9.3 8.1 −1.15 210412_at GRIN2B olfactoryreceptor, family 8, subfamily G, member 1 11 0.000888 5 4.5 −1.11216089_at MCFD2L — 12 0.000953 10 8.5 −1.18 226211_at MEG3 PRKC,apoptosis, WT1, regulator 13 0.001086 58.7 72.7 1.24 226856_at MUSTN1CUG triplet repeat, RNA binding protein 1 14 0.001156 11.7 14.7 1.26229671_s_at C21orf45 PBX/knotted 1 homeobox 1 15 0.001212 10 11.6 1.16219831_at CDKL3 cleavage stimulation factor, 3′ pre-RNA, subunit 2, 64kDa 16 0.001312 8.7 10 1.15 233429_at FLJ23577 matrix metallopeptidase 1(interstitial collagenase) 17 0.001349 14 19 1.36 210896_s_at ASPHIKAROS family zinc finger 1 (Ikaros) 18 0.001485 9.7 15 1.55 236901_atEST5 EPH receptor A1 19 0.001544 7.7 6.8 −1.13 213994_s_at SPON1fms-related tyrosine kinase 3 20 0.00155 11 9.5 −1.16 242417_atLOC283278 cytochrome P450, family 4, subfamily B, polypeptide 1 210.001565 6.3 5.6 −1.13 229777_at CLRN3 glutamate receptor, ionotropic,N-methyl D-aspartate 2B 22 0.001689 311.3 218.7 −1.42 205039_s_at IKZF1aspartate beta-hydroxylase 23 0.00176 18.8 22.5 1.20 204113_at CUGBP1nuclear factor of kappa light polypeptide gene enhancer in B-cells 2(p49/p100) 24 0.001934 11.6 14.8 1.28 233650_at CEP63 met proto-oncogene(hepatocyte growth factor receptor) 25 0.001951 42.8 57 1.33 236832_atLOC221442 spondin 1, extracellular matrix protein 26 0.001976 21.9 18.6−1.18 228721_at C3orf41 — 27 0.002036 6.9 8.9 1.29 226311_at EST6secretogranin III 28 0.002056 5.5 4.6 −1.20 1566428_at EST7cyclin-dependent kinase-like 3 29 0.002085 18.7 15 −1.25 229532_atZNF502 ankyrin repeat domain 55 30 0.002179 10.6 12 1.13 1554615_at EST8heparan-alpha-glucosaminide N-acetyltransferase 31 0.002264 5.9 5.4−1.09 230650_at EST9 family with sequence similarity 135, member A 320.00228 76.1 62.4 −1.22 204459_at CSTF2 maternally expressed 3(non-protein coding) 33 0.002381 5.3 4.8 −1.10 1570050_at EST10 — 340.002386 4.7 4.3 −1.09 1566096_x_at EST11 musculoskeletal, embryonicnuclear protein 1 35 0.002553 9 8 −1.13 1565407_at LHX9 hexokinasedomain containing 1 36 0.002585 5.1 5.6 1.10 232770_at TUSC3 — 370.002613 6.4 5.6 −1.14 204475_at MMP1 hypothetical protein LOC90784 380.002653 11.3 14.3 1.27 243349_at KIAA1324 thyroid hormone receptor,beta (erythroblastic leukemia viral (v-erb-a) oncogene homolog 2, avian)39 0.002726 5.7 5.1 −1.12 240604_at EXOD1 chromosome 3 open readingframe 41 40 0.002734 6 5.6 −1.07 210096_at CYP4B1 RNA binding proteinwith multiple splicing 2 41 0.00279 39.3 22 −1.79 228390_at EST12hypothetical protein LOC729680 42 0.002791 6.3 6.9 1.10 228977_atLOC729680 nuclear receptor subfamily 2, group F, member 2 43 0.0028229.5 10.6 1.12 213807_x_at MET zinc finger protein 502 44 0.002834 7.96.7 −1.18 228716_at THRB CDNA FLJ90800 fis, clone Y79AA1000127 450.002911 6.1 10.7 1.75 1560800_at EST13 clarin 3 46 0.00312 12.6 14.31.13 1567060_at OR8G1 — 47 0.003341 24.1 19.6 −1.23 223497_at FAM135ABetaine:homocysteine methyltransferase 48 0.003942 5.3 5.9 1.11211524_at NFKB2 tumor suppressor candidate 3 49 0.003954 14.2 12.3 −1.15241261_x_at EST14 sperm flagellar 2 50 0.003958 12.1 10.5 −1.15243048_at CECR7 centrosomal protein 63 kDa

TABLE E International Protein Index/UniGene Symbol Entrez Gene Name 1Hs.103854 DOK1 docking protein 1, 62 kDa (downstream of tyrosinekinase 1) 2 Hs.109752 C6ORF108 chromosome 6 open reading frame 108 3Hs.110675 APOC1 apolipoprotein C-I 4 Hs.116459 MAN2A2 mannosidase,alpha, class 2A, member 2 5 Hs.117331 TREML1 triggering receptorexpressed on myeloid cells-like 1 6 Hs.119177 ARF3 ADP-ribosylationfactor 3 7 Hs.123198 MYO9B myosin IXB 8 Hs.134084 M6PRmannose-6-phosphate receptor (cation dependent) 9 Hs.151135 FN3Kfructosamine 3 kinase 10 Hs.159509 SERPINF2 serpin peptidase inhibitor,clade F (alpha-2 antiplasmin, pigment epithelium derived factor), member2 11 Hs.190334 RAP1A RAP1A, member of RAS oncogene family 12 Hs.191215CYTH1 cytohesin 1 13 Hs.202 TSPO translocator protein (18 kDa) 14Hs.203637 PLS1 plastin 1 (I isoform) 15 Hs.226007 RDH11 retinoldehydrogenase 11 (all-trans/9-cis/11-cis) 16 Hs.24178 EML2 echinodermmicrotubule associated protein like 2 17 Hs.24258 GUCY1A3 guanylatecyclase 1, soluble, alpha 3 18 Hs.24889 FMN2 formin 2 19 Hs.260750 SNX12sorting nexin 12 20 Hs.277624 ZZEF1 zinc finger, ZZ-type with EF-handdomain 1 21 Hs.287714 RAB32 RAB32, member RAS oncogene family 22Hs.301412 UFC1 ubiquitin-fold modifier conjugating enzyme 1 23 Hs.306327RAB3GAP1 RAB3 GTPase activating protein subunit 1 (catalytic) 24Hs.327527 SMARCA4 SWI/SNF related, matrix associated, actin dependentregulator of chromatin, subfamily a, member 4 25 Hs.363396 CFHcomplement factor H 26 Hs.368078 DNAJA2 DnaJ (Hsp40) homolog, subfamilyA, member 2 27 Hs.368527 TOLLIP toll interacting protein 28 Hs.368626RTN1 reticulon 1 29 Hs.369840 NID2 nidogen 2 (osteonidogen) 30 Hs.376933GUK1 guanylate kinase 1 31 Hs.38449 SERPINE2 serpin peptidase inhibitor,clade E (nexin, plasminogen activator inhibitor type 1), member 2 32Hs.390567 FYN FYN oncogene related to SRC, FGR, YES 33 Hs.390667 GSTK1glutathione S-transferase kappa 1 34 Hs.411312 ITGA2B integrin, alpha 2b(platelet glycoprotein IIb of IIb/IIIa complex, antigen CD41) (includesEG: 3674) 35 Hs.414795 SERPINE1 serpin peptidase inhibitor, clade E(nexin, plasminogen activator inhibitor type 1), member 1 36 Hs.416848CTSW cathepsin W 37 Hs.420529 UBE2V1 ubiquitin-conjugating enzyme E2variant 1 38 Hs.429608 REEP5 receptor accessory protein 5 39 Hs.433068PRKAR2B protein kinase, cAMP-dependent, regulatory, type II, beta 40Hs.435291 ARHGAP6 Rho GTPase activating protein 6 41 Hs.435512 PPP3CAprotein phosphatase 3 (formerly 2B), catalytic subunit, alpha isoform 42Hs.438906 C22ORF30 chromosome 22 open reading frame 30 43 Hs.443976CEP250 centrosomal protein 250 kDa 44 Hs.458917 SCAMP2 secretory carriermembrane protein 2 45 Hs.460109 MYH11 myosin, heavy chain 11, smoothmuscle 46 Hs.462379 TOM1L2 target of myb1-like 2 (chicken) 47 Hs.464813PSMA8 proteasome (prosome, macropain) subunit, alpha type, 8 48Hs.465295 LMAN1 lectin, mannose-binding, 1 49 Hs.466910 CDA cytidinedeaminase 50 Hs.477009 USP24 ubiquitin specific peptidase 24 51Hs.477352 PDIA5 protein disulfide isomerase family A, member 5 52Hs.4779 GATAD2B GATA zinc finger domain containing 2B 53 Hs.480364METAP1 methionyl aminopeptidase 1 54 Hs.481836 MTMR12 myotubularinrelated protein 12 55 Hs.481860 TARS threonyl-tRNA synthetase 56Hs.482873 TMED5 transmembrane emp24 protein transport domain containing5 57 Hs.487540 RPA3 replication protein A3, 14 kDa 58 Hs.49582 PPP1R12Aprotein phosphatase 1, regulatory (inhibitor) subunit 12A 59 Hs.501200RGS10 regulator of G-protein signaling 10 60 Hs.502244 EIF3M eukaryotictranslation initiation factor 3, subunit M 61 Hs.50382 TJP2 tightjunction protein 2 (zona occludens 2) 62 Hs.506603 APPL2 adaptorprotein, phosphotyrosine interaction, PH domain and leucine zippercontaining 2 63 Hs.513055 WDR61 WD repeat domain 61 64 Hs.513646 IVDisovaleryl Coenzyme A dehydrogenase 65 Hs.514012 MAP2K3mitogen-activated protein kinase kinase 3 66 Hs.514199 VAT1 vesicleamine transport protein 1 homolog (T. californica) 67 Hs.514870 ATP5F1ATP synthase, H+ transporting, mitochondrial F0 complex, subunit B1 68Hs.520048 HLA-DRA major histocompatibility complex, class II, DR alpha69 Hs.524518 STAT6 signal transducer and activator of transcription 6,interleukin-4 induced 70 Hs.525419 LIMA1 LIM domain and actin binding 171 Hs.528952 TRIM25 tripartite motif-containing 25 72 Hs.529023 ZNF532zinc finger protein 532 73 Hs.530096 EIF3I (includes eukaryotictranslation initiation factor 3, subunit I EG: 8668) 74 Hs.573495SLC44A1 solute carrier family 44, member 1 75 Hs.578450 MESDC2 mesodermdevelopment candidate 2 76 Hs.584790 PPP2R1B protein phosphatase 2(formerly 2A), regulatory subunit A, beta isoform 77 Hs.592771 DGKGdiacylglycerol kinase, gamma 90 kDa 78 Hs.620557 ANK2 ankyrin 2,neuronal 79 Hs.631569 PPP1R14A protein phosphatase 1, regulatory(inhibitor) subunit 14A 80 Hs.63348 EMILIN1 elastin microfibrilinterfacer 1 80 Hs.63348 EMILIN1 elastin microfibril interfacer 1 81Hs.64016 PROS1 protein S (alpha) 82 Hs.647018 CLIP2 CAP-GLY domaincontaining linker protein 2 83 Hs.647064 RARRES2 retinoic acid receptorresponder (tazarotene induced) 2 84 Hs.653263 CEP110 centrosomal protein110 kDa 85 Hs.654404 HLA-C major histocompatibility complex, class I, C86 Hs.654439 APOE apolipoprotein E 87 Hs.654473 MAOB monoamine oxidase B88 Hs.654581 PRPS2 phosphoribosyl pyrophosphate synthetase 2 89Hs.654634 CDC42BPB CDC42 binding protein kinase beta (DMPK-like) 90Hs.655207 F2 coagulation factor II (thrombin) 91 Hs.655361 HPR (includeshaptoglobin-related protein EG: 3250) 92 Hs.656274 TNFAIP8 tumornecrosis factor, alpha-induced protein 8 93 Hs.656726 STRN striatin,calmodulin binding protein 94 Hs.658434 PSIP1 PC4 and SFRS1 interactingprotein 1 95 Hs.660130 CD226 CD226 molecule 96 Hs.695926 RASA1 RAS p21protein activator (GTPase activating protein) 1 97 Hs.696074 DHX15 DEAH(Asp-Glu-Ala-His) box polypeptide 15 98 Hs.696326 ANO6 anoctamin 6 99Hs.699154 LYN v-yes-1 Yamaguchi sarcoma viral related oncogene homolog100 Hs.7486 ETHE1 ethylmalonic encephalopathy 1 101 Hs.7753 CALUcalumenin 102 Hs.77741 KNG1 (includes kininogen 1 EG: 3827) 103 Hs.79322QARS glutaminyl-tRNA synthetase 104 Hs.8004 KALRN kalirin, RhoGEF kinase105 Hs.81934 ACADSB acyl-Coenzyme A dehydrogenase, short/branched chain106 Hs.90061 PGRMC1 progesterone receptor membrane component 1 107Hs.904 AGL amylo-1,6-glucosidase, 4-alpha-glucanotransferase 108IPI00010951 EPPK1 epiplakin 1 109 IPI00011891 PRKAA1 protein kinase,AMP-activated, alpha 1 catalytic subunit 110 IPI00165421 SERPINC1 serpinpeptidase inhibitor, clade C (antithrombin), member 1 111 IPI00301271RPN2 ribophorin II 112 IPI00382606 F7 coagulation factor VII (serumprothrombin conversion accelerator) 113 IPI00448925 IGHG1 immunoglobulinheavy constant gamma 1 (G1m marker) 114 IPI00783829 IPO5 importin 5 115IPI00787190 HLA-B major histocompatibility complex, class I, B 116IPI00788786 VWF von Willebrand factor 117 IPI00797856 HPSE heparanase

TABLE F International Protein Index/UniGene Symbol Entrez Gene Name 1IPI00001753 MYH4 myosin, heavy chain 4, skeletal muscle 2 Hs.110837TUBB4 tubulin, beta 4 3 Hs.132499 ARPC5L actin related protein 2/3complex, subunit 5-like (includes EG: 81873) 4 Hs.133892 TPM1tropomyosin 1 (alpha) 5 Hs.143046 CORO6 coronin 6 6 Hs.1437 GAAglucosidase, alpha; acid 7 Hs.143703 EHD4 EH-domain containing 4 8Hs.147433 PCNA proliferating cell nuclear antigen 9 Hs.148641 CTSHcathepsin H 10 Hs.154078 LBP lipopolysaccharide binding protein 11Hs.156367 RPS29 ribosomal protein S29 12 Hs.158339 SERPINB10 serpinpeptidase inhibitor, clade B (ovalbumin), member 10 13 Hs.161357 PDHB(includes pyruvate dehydrogenase (lipoamide) beta EG: 5162) 14 Hs.16355MYH10 myosin, heavy chain 10, non-muscle 15 Hs.163867 CD14 CD14 molecule16 Hs.164144 EIF5A2 eukaryotic translation initiation factor 5A2 17Hs.169284 PRPS1L1 phosphoribosyl pyrophosphate synthetase 1-like 1 18Hs.169900 PABPC4 poly(A) binding protein, cytoplasmic 4 (inducible form)19 Hs.170310 CECR1 cat eye syndrome chromosome region, candidate 1 20Hs.171626 SKP1 S-phase kinase-associated protein 1 21 Hs.173043 MTA2metastasis associated 1 family, member 2 22 Hs.188401 ANXA10 annexin A1023 Hs.189409 FNBP1 formin binding protein 1 24 Hs.196437 MOBKL1B MOB1,Mps One Binder kinase activator-like 1B (yeast) 25 Hs.200333 APOB48Rapolipoprotein B48 receptor 26 Hs.213470 PSMB7 proteasome (prosome,macropain) subunit, beta type, 7 27 Hs.220594 CCDC58 coiled-coil domaincontaining 58 28 Hs.224171 ENO3 enolase 3 (beta, muscle) 29 Hs.236030SMARCC2 SWI/SNF related, matrix associated, actin dependent regulator ofchromatin, subfamily c, (includes member 2 EG: 6601) 30 Hs.248746AGXT2L2 alanine-glyoxylate aminotransferase 2-like 2 31 Hs.252549 CTSZ(includes cathepsin Z EG: 1522) 32 Hs.258314 BRE brain and reproductiveorgan-expressed (TNFRSF1A modulator) 33 Hs.263812 NUDC nucleardistribution gene C homolog (A. nidulans) 34 Hs.268963 UBAP1 ubiquitinassociated protein 1 35 Hs.279640 TPR translocated promoter region (toactivated MET oncogene) 36 Hs.282901 RBM39 RNA binding motif protein 3937 Hs.284491 PDXK pyridoxal (pyridoxine, vitamin B6) kinase 38 Hs.309090SFRS7 splicing factor, arginine/serine-rich 7, 35 kDa 39 Hs.3100 KARSlysyl-tRNA synthetase 40 Hs.31053 TBCB tubulin folding cofactor B 41Hs.319334 NASP nuclear autoantigenic sperm protein (histone-binding) 42Hs.325978 NUMA1 nuclear mitotic apparatus protein 1 43 Hs.335034 DPYDdihydropyrimidine dehydrogenase 44 Hs.337766 RPL18A ribosomal proteinL18a 45 Hs.3439 STOML2 stomatin (EPB72)-like 2 46 Hs.356604 WNK1 WNKlysine deficient protein kinase 1 47 Hs.368077 SERPINB8 serpin peptidaseinhibitor, clade B (ovalbumin), member 8 48 Hs.368203 DOCK11 dedicatorof cytokinesis 11 49 Hs.368266 CLTCL1 clathrin, heavy chain-like 1 50Hs.36927 HSPH1 heat shock 105 kDa/110 kDa protein 1 51 Hs.369373 SEC23BSec23 homolog B (S. cerevisiae) 52 Hs.375957 ITGB2 integrin, beta 2(complement component 3 receptor 3 and 4 subunit) 53 Hs.376933 GUK1guanylate kinase 1 54 Hs.388664 RPL11 ribosomal protein L11 55 Hs.403436DCI dodecenoyl-Coenzyme A delta isomerase (3,2 trans-enoyl-Coenzyme Aisomerase) 56 Hs.406423 SF3B2 splicing factor 3b, subunit 2, 145 kDa 57Hs.407190 FKBP5 FK506 binding protein 5 58 Hs.408061 FABP5 fatty acidbinding protein 5 (psoriasis-associated) 59 Hs.408236 TXNDC17thioredoxin domain containing 17 60 Hs.409834 PHPT1 phosphohistidinephosphatase 1 61 Hs.412117 ANXA6 annexin A6 62 Hs.429180 EIF2S2eukaryotic translation initiation factor 2, subunit 2 beta, 38 kDa 63Hs.432674 LARS leucyl-tRNA synthetase 64 Hs.433222 NPC2 Niemann-Pickdisease, type C2 65 Hs.434996 GIT2 G protein-coupled receptor kinaseinteracting ArfGAP 2 66 Hs.437385 NECAP2 NECAP endocytosis associated 267 Hs.440895 MYH3 myosin, heavy chain 3, skeletal muscle, embryonic 68Hs.440932 9-Sep septin 9 69 Hs.460002 FLJ11151 hypothetical proteinFLJ11151 70 Hs.461925 RPA1 replication protein A1, 70 kDa 71 Hs.465224NARS asparaginyl-tRNA synthetase 72 Hs.465761 ARHGEF18 rho/rac guaninenucleotide exchange factor (GEF) 18 73 Hs.465924 SDHB (includessuccinate dehydrogenase complex, subunit B, iron sulfur (lp) EG: 6390)74 Hs.470627 LCK lymphocyte-specific protein tyrosine kinase 75Hs.471207 NDUFS1 NADH dehydrogenase (ubiquinone) Fe—S protein 1, 75 kDa(NADH-coenzyme Q reductase) 76 Hs.477126 ATG3 ATG3 autophagy related 3homolog (S. cerevisiae) 77 Hs.484412 EXOC2 exocyst complex component 278 Hs.491440 PPP2CB protein phosphatase 2 (formerly 2A), catalyticsubunit, beta isoform 79 Hs.494496 FBP1 fructose-1,6-bisphosphatase 1 80Hs.494595 TMOD1 tropomodulin 1 81 Hs.497599 WARS tryptophanyl-tRNAsynthetase 82 Hs.502328 CD44 CD44 molecule (Indian blood group) 83Hs.502756 AHNAK AHNAK nucleoprotein 84 Hs.505033 KRAS v-Ki-ras2 Kirstenrat sarcoma viral oncogene homolog 85 Hs.5086 RBM42 RNA binding motifprotein 42 86 Hs.508738 ARHGEF7 Rho guanine nucleotide exchange factor(GEF) 7 87 Hs.509736 HSP90AB1 heat shock protein 90 kDa alpha(cytosolic), class B member 1 88 Hs.513726 GBP5 guanylate bindingprotein 5 89 Hs.514495 SRP68 signal recognition particle 68 kDa 90Hs.514581 ACTG1 actin, gamma 1 91 Hs.517307 MX1 myxovirus (influenzavirus) resistance 1, interferon-inducible protein p78 (mouse) 92Hs.517949 MAP4 microtubule-associated protein 4 93 Hs.518198 CSTA(includes cystatin A (stefin A) EG: 1475) 94 Hs.518662 FAM129A familywith sequence similarity 129, member A 95 Hs.521924 PUF60 poly-U bindingsplicing factor 60 KDa 96 Hs.529989 RNASET2 ribonuclease T2 97 Hs.531176SARS seryl-tRNA synthetase 98 Hs.531807 ARHGAP25 Rho GTPase activatingprotein 25 99 Hs.534350 SMARCB1 SWI/SNF related, matrix associated,actin dependent regulator of chromatin, subfamily b, member 1 100Hs.534770 PKM2 pyruvate kinase, muscle 101 Hs.535581 TPM3 tropomyosin 3102 Hs.55682 EIF3D eukaryotic translation initiation factor 3, subunit D103 Hs.583855 SNX6 sorting nexin 6 104 Hs.587558 NCF2 neutrophilcytosolic factor 2 105 Hs.591176 DYNLL2 dynein, light chain, LC8-type 2106 Hs.591768 BTF3 basic transcription factor 3 107 Hs.591922 SLKSTE20-like kinase (yeast) 108 Hs.632733 ALDH2 aldehyde dehydrogenase 2family (mitochondrial) 109 Hs.643487 ACAA1 acetyl-Coenzyme Aacyltransferase 1 110 Hs.649475 RPL24 ribosomal protein L24 111Hs.654404 HLA-C major histocompatibility complex, class I, C 112Hs.654408 NFKB1 nuclear factor of kappa light polypeptide gene enhancerin B-cells 1 113 Hs.654429 SEC24C SEC24 family, member C (S. cerevisiae)(includes EG: 9632) 114 Hs.654521 WIPF1 WAS/WASL interacting proteinfamily, member 1 115 Hs.654543 TUBB2A tubulin, beta 2A 116 Hs.654597ACAP2 ArfGAP with coiled-coil, ankyrin repeat and PH domains 2 117Hs.655196 HP haptoglobin 118 Hs.656726 STRN striatin, calmodulin bindingprotein 119 Hs.656870 SLC25A24 solute carrier family 25 (mitochondrialcarrier; phosphate carrier), member 24 120 Hs.687055 PARP14 poly(ADP-ribose) polymerase family, member 14 121 Hs.68714 SFRS1 splicingfactor, arginine/serine-rich 1 122 Hs.690634 HSPA1L heat shock 70 kDaprotein 1-like 123 Hs.69293 HEXB hexosaminidase B (beta polypeptide) 124Hs.695973 HNRNPK heterogeneous nuclear ribonucleoprotein K 125 Hs.699408CLINT1 clathrin interactor 1 126 Hs.699441 NFATC2 nuclear factor ofactivated T-cells, cytoplasmic, calcineurin-dependent 2 127 Hs.73839RNASE3 ribonuclease, RNase A family, 3 (eosinophil cationic protein) 128Hs.74368 CKAP4 cytoskeleton-associated protein 4 129 Hs.77254 CBX1chromobox homolog 1 (HP1 beta homolog Drosophila) 130 Hs.77897 SF3A3splicing factor 3a, subunit 3, 60 kDa 131 Hs.78880 ILVBL ilvB (bacterialacetolactate synthase)-like 132 Hs.79110 NCL nucleolin 133 Hs.8360C11ORF54 chromosome 11 open reading frame 54 134 Hs.83753 SNRPB smallnuclear ribonucleoprotein polypeptides B and B1 135 Hs.861 MAPK3mitogen-activated protein kinase 3 136 Hs.99936 KRT10 keratin 10 137IPI00074489 NDUFB10 NADH dehydrogenase (ubiquinone) 1 beta subcomplex,10, 22 kDa 138 IPI00384938 IGHG1 immunoglobulin heavy constant gamma 1(G1m marker) 139 IPI00396421 KIAA0776 KIAA0776 140 IPI00401105 RPS25ribosomal protein S25 141 IPI00413108 RPSA (includes ribosomal proteinSA EG: 3921) 142 IPI00456853 FAM21C family with sequence similarity 21,member C 143 IPI00465022 SMCHD1 structural maintenance of chromosomesflexible hinge domain containing 1

TABLE G Fold Change International (positive numbers Protein areupregulated Index/UniGene Symbol Entrez Gene Name in B1) 1 Hs.180062PSMB8 proteasome (prosome, macropain) subunit, beta type, 8 (large1.74748 multifunctional peptidase 7) 2 IPI00001539 ACAA2 acetyl-CoenzymeA acyltransferase 2 2.53112 3 Hs.412117 ANXA6 annexin A6 1.99146 4Hs.90093 HSPA4 heat shock 70 kDa protein 4 2.72271 5 Hs.130316 DBN1drebrin 1 −2.19867 6 IPI00003438 DNAJC8 DnaJ (Hsp40) homolog, subfamilyC, member 8 2.74556 7 Hs.186350 RPL4 ribosomal protein L4 1.80696 8Hs.175437 EPB41 erythrocyte membrane protein band 4.1 (elliptocytosis 1,RH-linked) 1.37195 9 Hs.2178 HIST2H2BE histone cluster 2, H2be 1.7389310 Hs.524630 UBE2N ubiquitin-conjugating enzyme E2N (UBC13 homolog,yeast) 2.17574 11 Hs.411695 HK3 hexokinase 3 (white cell) 2.79458 12Hs.489284 ARPC1B actin related protein 2/3 complex, subunit 1B, 41 kDa1.87474 13 Hs.514934 CAPZA1 capping protein (actin filament) muscleZ-line, alpha 1 1.77014 14 Hs.431279 NSF N-ethylmaleimide-sensitivefactor 4.20439 15 Hs.155975 PTPRCAP protein tyrosine phosphatase,receptor type, C-associated protein −1.77658 16 Hs.458272 MPOmyeloperoxidase 1.71345 17 Hs.433615 TUBB2C tubulin, beta 2C −1.76403 18Hs.184233 HSPA9 heat shock 70 kDa protein 9 (mortalin) 6.35072 19Hs.295917 ATP6V1B2 ATPase, H+ transporting, lysosomal 56/58 kDa, V1subunit B2 2.24142 20 Hs.521640 RAD23B RAD23 homolog B (S. cerevisiae)1.96378 21 Hs.699880 RPS10 ribosomal protein S10 3.17111 22 Hs.546285RPLP0 (includes ribosomal protein, large, P0 2.03495 EG: 6175) 23Hs.389649 EIF4A3 (includes eukaryotic translation initiation factor 4A,isoform 3 1.89742 EG: 9775) 24 Hs.511251 SQRDL (includes sulfide quinonereductase-like (yeast) 2.33602 EG: 58472) 25 Hs.26010 PFKPphosphofructokinase, platelet −2.73727 26 Hs.78888 DBI diazepam bindinginhibitor (GABA receptor modulator, acyl-Coenzyme 2.47829 A bindingprotein) 27 Hs.405144 SFRS3 splicing factor, arginine/serine-rich 34.47655 28 Hs.413812 RAC1 ras-related C3 botulinum toxin substrate 1(rho family, small GTP 2.76246 binding protein Rac1) 29 Hs.558351 KIF2Akinesin heavy chain member 2A −1.41796 30 Hs.355934 SFPQ splicing factorproline/glutamine-rich (polypyrimidine tract binding 2.45856 proteinassociated) 31 Hs.464336 P4HB prolyl 4-hydroxylase, beta polypeptide2.20506 32 Hs.131151 PSMD9 proteasome (prosome, macropain) 26S subunit,non-ATPase, 9 −1.67257 33 Hs.247362 DDAH2 dimethylargininedimethylaminohydrolase 2 1.98084 34 Hs.356654 PSMC1 proteasome (prosome,macropain) 26S subunit, ATPase, 1 2.36445 35 Hs.527105 HNRPDLheterogeneous nuclear ribonucleoprotein D-like 5.14561 36 Hs.472838 STK4serine/threonine kinase 4 1.65603 37 Hs.373763 HNRNPR heterogeneousnuclear ribonucleoprotein R 3.23939 38 Hs.440898 FCN1 ficolin(collagen/fibrinogen domain containing) 1 3.12337 39 Hs.178551 RPL8ribosomal protein L8 2.39479 40 Hs.644646 KIF5B kinesin family member 5B−1.81795 41 Hs.153837 MNDA myeloid cell nuclear differentiation antigen2.21411 42 Hs.627414 RPS18 ribosomal protein S18 2.94127 43 Hs.546287RPS7 ribosomal protein S7 1.83705 44 Hs.497788 EPRS glutamyl-prolyl-tRNAsynthetase 1.99658 45 Hs.511743 TUBB3 tubulin, beta 3 −1.48195 46Hs.270291 ACTN4 actinin, alpha 4 2.09181 47 Hs.119251 UQCRC1ubiquinol-cytochrome c reductase core protein I 2.05968 48 Hs.699298CDV3 CDV3 homolog (mouse) 1.35707 49 Hs.111779 SPARC secreted protein,acidic, cysteine-rich (osteonectin) −3.78710 50 Hs.651923 CNN2 calponin2 2.25485 51 Hs.465511 GZMM granzyme M (lymphocyte met-ase 1) 2.38354 52Hs.2853 PCBP1 (includes poly(rC) binding protein 1 1.65937 EG: 5093) 53Hs.690198 CDC42 cell division cycle 42 (GTP binding protein, 25 kDa)1.59084 54 Hs.271510 GSR glutathione reductase 2.59620 55 Hs.406277SF3A1 splicing factor 3a, subunit 1, 120 kDa 2.92334 56 Hs.571177SYNCRIP synaptotagmin binding, cytoplasmic RNA interacting protein3.05703 57 Hs.695941 HK1 hexokinase 1 1.48167 58 Hs.250758 PSMC3proteasome (prosome, macropain) 26S subunit, ATPase, 3 1.90255 59 Hs.707KRT2 keratin 2 3.19828 60 Hs.594444 LMNA lamin A/C 2.42545 61 Hs.2490CASP1 caspase 1, apoptosis-related cysteine peptidase (interleukin 1,beta, 2.18090 convertase) 62 Hs.75307 H1FX H1 histone family, member X2.60755 63 Hs.534639 HADHB hydroxyacyl-Coenzyme Adehydrogenase/3-ketoacyl-Coenzyme A 2.04804 thiolase/enoyl-Coenzyme Ahydratase (trifunctional protein), beta subunit 64 Hs.30054 F5coagulation factor V (proaccelerin, labile factor) −2.31510 65 Hs.533040PDLIM7 PDZ and LIM domain 7 (enigma) −2.15116 66 Hs.665429 DDX17 DEAD(Asp-Glu-Ala-Asp) box polypeptide 17 2.97738 67 Hs.695185 NAP1L1nucleosome assembly protein 1-like 1 −1.56121 68 Hs.75841 ERP29endoplasmic reticulum protein 29 3.53236 69 Hs.523302 PRDX3peroxiredoxin 3 1.71589 70 IPI00024989 PCMT1 protein-L-isoaspartate(D-aspartate) O-methyltransferase 2.22172 71 Hs.430606 CS citratesynthase −2.53628 72 Hs.520973 HSPB1 heat shock 27 kDa protein 1 1.8940673 Hs.118958 STX11 syntaxin 11 −1.57367 74 Hs.610830 PRKCSH proteinkinase C substrate 80K-H 2.25450 75 Hs.14601 HCLS1 hematopoieticcell-specific Lyn substrate 1 2.13579 76 Hs.632828 HNRNPH2 heterogeneousnuclear ribonucleoprotein H2 (H′) 3.09381 77 Hs.694128 RPS14 ribosomalprotein S14 2.10304 78 Hs.356624 NID1 nidogen 1 −4.10930 79 Hs.12084TUFM Tu translation elongation factor, mitochondrial 1.77413 80 Hs.95990PKLR pyruvate kinase, liver and RBC 2.55932 81 Hs.654614 HSPA6 heatshock 70 kDa protein 6 (HSP70B′) 1.28057 82 Hs.471441 PSMB2 proteasome(prosome, macropain) subunit, beta type, 2 3.18295 83 Hs.7744 NDUFV1NADH dehydrogenase (ubiquinone) flavoprotein 1, 51 kDa 2.82524 84Hs.480073 HNRNPD heterogeneous nuclear ribonucleoprotein D (AU-richelement RNA 2.72172 binding protein 1, 37 kDa) 85 Hs.98791 ACTR1B(includes ARP1 actin-related protein 1 homolog B, centractin beta(yeast) 3.00772 EG: 10120) 86 IPI00029625 FLOT2 flotillin 2 3.53456 87Hs.11355 TMPO thymopoietin 3.65290 88 Hs.571841 RPL7 ribosomal proteinL7 1.81095 89 Hs.699271 STAT1 signal transducer and activator oftranscription 1, 91 kDa 2.36973 90 Hs.529451 DIAPH1 diaphanous homolog 1(Drosophila) 1.44181 91 Hs.516032 HADHA hydroxyacyl-Coenzyme Adehydrogenase/3-ketoacyl-Coenzyme A 4.43165 thiolase/enoyl-Coenzyme Ahydratase (trifunctional protein), alpha subunit 92 Hs.503043 CPT1Acarnitine palmitoyltransferase 1A (liver) −1.45507 93 Hs.475074 PARVBparvin, beta −1.93236 94 Hs.655396 PSMD11 proteasome (prosome,macropain) 26S subunit, non-ATPase, 11 1.89081 95 Hs.122523 SND1staphylococcal nuclease and tudor domain containing 1 2.96927 96Hs.444075 UBASH3B ubiquitin associated and SH3 domain containing, B−1.85814 97 Hs.473144 CASS4 Cas scaffolding protein family member 4−2.58235 98 Hs.436186 CAST calpastatin 1.48337 99 Hs.465808 HNRNPMheterogeneous nuclear ribonucleoprotein M 2.64995 100 Hs.506759 ATP2A2ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 −1.44671 101Hs.535581 TPM3 tropomyosin 3 2.05422 102 Hs.654720 KIAA1967 KIAA19673.42772 103 Hs.515517 RPL18 ribosomal protein L18 3.72595 104 Hs.438429RPS19 ribosomal protein S19 4.78644 105 IPI00216134 TPM1 tropomyosin 1(alpha) −1.36995 106 Hs.128548 WDR1 WD repeat domain 1 4.48437 107Hs.519320 VDAC1 voltage-dependent anion channel 1 1.94443 108 Hs.512675RPS8 ribosomal protein S8 3.35144 109 IPI00216633 EPB49 erythrocytemembrane protein band 4.9 (dematin) −1.84863 110 Hs.496622 PLS3 plastin3 (T isoform) 3.79198 111 Hs.654438 ANK1 ankyrin 1, erythrocytic 2.45336112 Hs.417303 SPTB spectrin, beta, erythrocytic 1.95917 113 Hs.89497LMNB1 lamin B1 2.53206 114 Hs.172631 ITGAM integrin, alpha M (complementcomponent 3 receptor 3 subunit) 6.14877 115 Hs.652308 MTHFD1methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1, 1.36675methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolatesynthetase 116 Hs.411312 ITGA2B (includes integrin, alpha 2b (plateletglycoprotein IIb of IIb/IIIa complex, antigen 3.09010 EG: 3674) CD41)117 Hs.76392 ALDH1A1 aldehyde dehydrogenase 1 family, member A1 −1.59383118 Hs.500756 GOT1 glutamic-oxaloacetic transaminase 1, soluble(aspartate 1.42300 aminotransferase 1) 119 Hs.514196 RPL27 ribosomalprotein L27 2.67384 120 Hs.445351 LGALS1 lectin, galactoside-binding,soluble, 1 2.14691 121 Hs.80828 KRT1 keratin 1 3.95879 122 Hs.654559HNRNPL heterogeneous nuclear ribonucleoprotein L −3.40543 123 Hs.119825SPTA1 spectrin, alpha, erythrocytic 1 (elliptocytosis 2) 1.66210 124Hs.446588 RPS13 ribosomal protein S13 3.62921 125 Hs.433427 RPS17(includes ribosomal protein S17 4.39840 EG: 6218) 126 Hs.483305 HINT1histidine triad nucleotide binding protein 1 −2.04047 127 Hs.476448 FLNBfilamin B, beta (actin binding protein 278) −1.82786 128 Hs.350899 CAPN2calpain 2, (m/II) large subunit 2.86704 129 Hs.520967 MDH2 malatedehydrogenase 2, NAD (mitochondrial) 2.20250 130 Hs.371563 RAB14 RAB14,member RAS oncogene family 1.66010 131 Hs.83722 EPS15 epidermal growthfactor receptor pathway substrate 15 2.14994 132 Hs.580681 SAMHD1 SAMdomain and HD domain 1 2.17687 133 Hs.88778 CBR1 carbonyl reductase 11.69648 134 Hs.497599 WARS tryptophanyl-tRNA synthetase 1.58361 135Hs.517622 UNC84B unc-84 homolog B (C. elegans) 1.78160 136 Hs.523145DDOST dolichyl-diphosphooligosaccharide-protein glycosyltransferase1.71412 137 Hs.539684 EIF2S3 eukaryotic translation initiation factor 2,subunit 3 gamma, 52 kDa 2.09125 138 Hs.201978 PTGS1prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase−1.72382 and cyclooxygenase) 139 Hs.370770 XPO1 exportin 1 (CRM1homolog, yeast) 2.13295 140 Hs.696016 SNX2 sorting nexin 2 1.83066 141Hs.181301 CTSS cathepsin S 2.66342 142 Hs.204238 LCN2 lipocalin 2−2.88567 143 Hs.212102 PDIA6 protein disulfide isomerase family A,member 6 2.67256 144 Hs.465041 HDHD2 haloacid dehalogenase-likehydrolase domain containing 2 1.58049 145 Hs.125113 CCT8 chaperonincontaining TCP1, subunit 8 (theta) 2.74083 146 Hs.218040 ITGB3 integrin,beta 3 (platelet glycoprotein IIIa, antigen CD61) −2.86872 147 Hs.126941FAM49B family with sequence similarity 49, member B 2.41970 148Hs.140452 M6PRBP1 mannose-6-phosphate receptor binding protein 1 2.45483149 Hs.591940 APOA4 apolipoprotein A-IV 2.29544 150 Hs.519756 STK10serine/threonine kinase 10 2.91394 151 Hs.274402 HSPA1A heat shock 70kDa protein 1A 3.13788 152 Hs.571886 AKR7A2 aldo-keto reductase family7, member A2 (aflatoxin aldehyde 2.51928 reductase) 153 Hs.599481 EIF4A2eukaryotic translation initiation factor 4A, isoform 2 3.52387 154Hs.352224 EDARADD EDAR-associated death domain 7.46803 155 Hs.534385THOC4 THO complex 4 −1.32827 156 Hs.528668 RPL6 ribosomal protein L63.03691 157 Hs.368084 LRPPRC leucine-rich PPR-motif containing −1.71518158 Hs.632717 MYL6 myosin, light chain 6, alkali, smooth muscle andnon-muscle 3.02347 159 Hs.482043 NNT nicotinamide nucleotidetranshydrogenase 2.26497 160 Hs.525600 HSP90AA1 heat shock protein 90kDa alpha (cytosolic), class A member 1 2.84841 161 Hs.513530 TGFB1I1transforming growth factor beta 1 induced transcript 1 −2.45685 162Hs.369920 RAP1B RAP1B, member of RAS oncogene family −2.37368 163Hs.148340 RPL10A (includes ribosomal protein L10a 1.99620 EG: 4736) 164Hs.200716 MECP2 methyl CpG binding protein 2 (Rett syndrome) 2.99376 165Hs.642813 VIM vimentin 1.75207 166 Hs.570791 LAP3 leucine aminopeptidase3 2.49300 167 Hs.516539 HNRNPA3 heterogeneous nuclear ribonucleoproteinA3 1.70158 168 Hs.356572 RPS3A ribosomal protein S3A 3.02357 169Hs.518530 PAK2 p21 protein (Cdc42/Rac)-activated kinase 2 2.61046 170Hs.37617 MYO1G myosin IG 2.16324 171 Hs.467408 TRIM28 tripartitemotif-containing 28 2.84983 172 Hs.136905 HUWE1 HECT, UBA and WWE domaincontaining 1 1.88641 173 IPI00464990 GP1BB glycoprotein Ib (platelet),beta polypeptide −1.88206 174 Hs.617193 CYCS (includes cytochrome c,somatic 1.64385 EG: 54205) 175 Hs.595053 HSPD1 heat shock 60 kDa protein1 (chaperonin) 1.76318 176 Hs.534770 PKM2 pyruvate kinase, muscle1.27869 177 Hs.166463 HNRNPU heterogeneous nuclear ribonucleoprotein U(scaffold attachment factor 2.79696 A) 178 Hs.2533 ALDH9A1 aldehydedehydrogenase 9 family, member A1 1.38474 179 Hs.700575 STMN1 stathmin1/oncoprotein 18 2.31540 180 Hs.530687 RNH1 ribonuclease/angiogenininhibitor 1 1.64737 181 Hs.696144 TXNRD1 thioredoxin reductase 1 1.70635182 Hs.502756 AHNAK AHNAK nucleoprotein 6.50929 183 Hs.10842 RAN RAN,member RAS oncogene family 2.05198 184 Hs.311609 DDX39 DEAD(Asp-Glu-Ala-Asp) box polypeptide 39 2.85922 185 Hs.533273 UBA1ubiquitin-like modifier activating enzyme 1 1.88773 186 Hs.695946 ITGB1integrin, beta 1 (fibronectin receptor, beta polypeptide, antigen CD29−3.90341 includes MDF2, MSK12) 187 IPI00646888 1-Sep septin 1 2.21854188 Hs.546292 RPS27A ribosomal protein S27a −1.51316

TABLE H International Protein Index/ UniGene Symbol Entrez Gene Name 1Hs.1012 C4BPA complement component 4 binding protein, alpha 2 Hs.110675APOC1 apolipoprotein C-I 3 Hs.116448 GLS Glutaminase 4 Hs.191215 CYTH1cytohesin 1 5 Hs.202 TSPO translocator protein (18 kDa) 6 Hs.203637 PLS1plastin 1 (I isoform) 7 Hs.24889 FMN2 formin 2 8 Hs.327527 SMARCA4SWI/SNF related, matrix associated, actin dependent regulator ofchromatin, subfamily a, member 4 9 Hs.352224 EDARADD EDAR-associateddeath domain 10 Hs.464813 PSMA8 proteasome (prosome, macropain) subunit,alpha type, 8 11 Hs.466910 CDA cytidine deaminase 12 Hs.4779 GATAD2BGATA zinc finger domain containing 2B 13 Hs.482873 TMED5 transmembraneemp24 protein transport domain containing 5 14 Hs.501200 RGS10 regulatorof G-protein signaling 10 15 Hs.518750 OCIAD1 OCIA domain containing 116 Hs.529023 ZNF532 zinc finger protein 532 17 Hs.594444 LMNA lamin A/C18 Hs.620557 ANK2 ankyrin 2, neuronal 19 Hs.653263 CEP110 centrosomalprotein 110 kDa 20 Hs.654438 ANK1 ankyrin 1, erythrocytic 21 Hs.69771CFB complement factor B 22 Hs.77741 KNG1 kininogen 1 (includes EG: 3827)23 Hs.83634 HCFC1 host cell factor C1 (VP16-accessory protein) 24IPI00010951 EPPK1 epiplakin 1 25 IPI00382606 F7 coagulation factor VII(serum prothrombin conversion accelerator) 26 IPI00641229 IGHA2immunoglobulin heavy constant alpha 2 (A2m marker) 27 IPI00645452 TUBBtubulin, beta 28 IPI00787190 HLA-B major histocompatibility complex,class I, B

TABLE I Unigene/IPI Symbol Entrez Gene Name 1 Hs.406758 HIBADH3-hydroxyisobutyrate dehydrogenase 2 Hs.656685 HIBCH3-hydroxyisobutyryl-Coenzyme A hydrolase 3 Hs.643487 ACAA1acetyl-Coenzyme A acyltransferase 1 4 Hs.558296 ACP1 acid phosphatase 1,soluble 5 Hs.514581 ACTG1 actin, gamma 1 6 Hs.461727 ACSF3 acyl-CoAsynthetase family member 3 7 Hs.464137 ACOX1 acyl-Coenzyme A oxidase 1,palmitoyl 8 Hs.512815 AP3D1 adaptor-related protein complex 3, delta 1subunit 9 Hs.470907 AK2 adenylate kinase 2 10 Hs.525330 ARF6ADP-ribosylation factor 6 11 Hs.62578 ARFGEF2 ADP-ribosylation factorguanine nucleotide-exchange factor 2 (brefeldin A-inhibited) 12Hs.418167 ALB albumin 13 Hs.632733 ALDH2 aldehyde dehydrogenase 2 family(mitochondrial) 14 Hs.591631 AGPS alkylglycerone phosphate synthase 15Hs.499725 ANK3 ankyrin 3, node of Ranvier (ankyrin G) 16 Hs.696087ANKFY1 ankyrin repeat and FYVE domain containing 1 17 Hs.412117 ANXA6annexin A6 18 Hs.3346 ANXA9 annexin A9 19 Hs.435771 API5 apoptosisinhibitor 5 20 Hs.503165 ARAP1 ArfGAP with RhoGAP domain, ankyrin repeatand PH domain 1 21 Hs.465224 NARS asparaginyl-tRNA synthetase 22Hs.477126 ATG3 ATG3 autophagy related 3 homolog (S. cerevisiae) 23Hs.486063 ATG5 (includes ATG5 autophagy related 5 homolog (S.cerevisiae) EG: 9474) 24 Hs.584905 ATL1 atlastin GTPase 1 25 Hs.85539ATP5I ATP synthase, H+ transporting, mitochondrial F0 complex, subunit E26 Hs.656515 ATP5J2 ATP synthase, H+ transporting, mitochondrial F0complex, subunit F2 27 Hs.444957 ATP8A2 ATPase, aminophospholipidtransporter-like, class I, type 8A, member 2 28 Hs.517338 ATP6V1E1ATPase, H+ transporting, lysosomal 31 kDa, V1 subunit E1 29 Hs.491737ATP6V1H ATPase, H+ transporting, lysosomal 50/57 kDa, V1 subunit H 30Hs.429294 ABCA1 ATP-binding cassette, sub-family A (ABC1), member 1 31Hs.508423 ABCC4 ATP-binding cassette, sub-family C (CFTR/MRP), member 432 Hs.355983 BZW1 basic leucine zipper and W2 domains 1 33 Hs.591768BTF3 basic transcription factor 3 34 Hs.494614 BAT2D1 BAT2 domaincontaining 1 35 Hs.631546 BAX BCL2-associated X protein 36 Hs.654740BRWD1 bromodomain and WD repeat domain containing 1 37 Hs.418533 BUB3budding uninhibited by benzimidazoles 3 homolog (yeast) 38 IPI00797310CLSTN3 calsyntenin 3 39 Hs.524809 CLIP1 CAP-GLY domain containing linkerprotein 1 40 Hs.699182 CPT2 carnitine palmitoyltransferase 2 41Hs.504096 CBL Cas-Br-M (murine) ecotropic retroviral transformingsequence 42 Hs.654616 CASP6 caspase 6, apoptosis-related cysteinepeptidase 43 Hs.460232 CNOT1 CCR4-NOT transcription complex, subunit 144 Hs.485518 CD2AP CD2-associated protein 45 Hs.502328 CD44 CD44molecule (Indian blood group) 46 Hs.556638 CISD2 CDGSH iron sulfurdomain 2 47 Hs.472027 CDS2 CDP-diacylglycerol synthase (phosphatidatecytidylyltransferase) 2 48 Hs.568242 CREG1 cellular repressor ofE1A-stimulated genes 1 49 Hs.31819 C1ORF128 chromosome 1 open readingframe 128 50 Hs.368353 C1ORF71 chromosome 1 open reading frame 71 51Hs.611057 C1ORF77 chromosome 1 open reading frame 77 52 Hs.462033C1ORF93 chromosome 1 open reading frame 93 53 Hs.8360 C11ORF54chromosome 11 open reading frame 54 54 Hs.530753 C11ORF59 chromosome 11open reading frame 59 55 IPI00373869 C17ORF49 chromosome 17 open readingframe 49 56 Hs.368266 CLTCL1 clathrin, heavy chain-like 1 57 Hs.591506MYCBP c-myc binding protein 58 Hs.505652 COPZ1 coatomer protein complex,subunit zeta 1 59 Hs.655010 CHCHD3 coiled-coil-helix-coiled-coil-helixdomain containing 3 60 Hs.369614 COPS2 COP9 constitutivephotomorphogenic homolog subunit 2 (Arabidopsis) 61 Hs.502917 CCS copperchaperone for superoxide dismutase 62 Hs.460923 CBFB core-bindingfactor, beta subunit 63 Hs.372286 CUL3 cullin 3 64 Hs.518198 CSTA(includes cystatin A (stefin A) EG: 1475) 65 Hs.481898 CCBL2 cysteineconjugate-beta lyase 2 66 Hs.513803 CYBA cytochrome b-245, alphapolypeptide 67 Hs.461131 CYB5B cytochrome b5 type B (outer mitochondrialmembrane) 68 IPI00017510 COX2 cytochrome c oxidase II 69 Hs.696092CLASP2 cytoplasmic linker associated protein 2 70 Hs.99120 DDX3Y DEAD(Asp-Glu-Ala-Asp) box polypeptide 3, Y-linked (includes EG: 8653) 71Hs.75189 DAP death-associated protein 72 Hs.368203 DOCK11 dedicator ofcytokinesis 11 73 Hs.654567 DENND4A DENN/MADD domain containing 4A 74Hs.407618 DSG4 desmoglein 4 75 Hs.9857 DCXR dicarbonyl/L-xylulosereductase 76 Hs.335551 DLAT dihydrolipoamide S-acetyltransferase 77Hs.37916 DPP7 dipeptidyl-peptidase 7 78 Hs.515210 DNAJB1 DnaJ (Hsp40)homolog, subfamily B, member 1 79 Hs.656476 DNAJC3 DnaJ (Hsp40) homolog,subfamily C, member 3 80 Hs.425801 DUSP23 dual specificity phosphatase23 81 Hs.522413 DNM1 dynamin 1 82 Hs.529495 DYNC1LI1 dynein, cytoplasmic1, light intermediate chain 1 83 Hs.591176 DYNLL2 dynein, light chain,LC8-type 2 84 Hs.4747 DKC1 dyskeratosis congenita 1, dyskerin 85Hs.412103 EFHA1 EF-hand domain family, member A1 86 Hs.654553 ETFB(includes electron-transfer-flavoprotein, beta polypeptide EG: 2109) 87Hs.509791 ERH enhancer of rudimentary homolog (Drosophila) 88 Hs.429879EHHADH enoyl-Coenzyme A, hydratase/3-hydroxyacyl Coenzyme Adehydrogenase 89 Hs.419815 EGF epidermal growth factor(beta-urogastrone) 90 Hs.477498 EEFSEC eukaryotic elongation factor,selenocysteine-tRNA-specific 91 Hs.429180 EIF2S2 eukaryotic translationinitiation factor 2, subunit 2 beta, 38 kDa 92 Hs.696322 EIF2C2eukaryotic translation initiation factor 2C, 2 93 Hs.55682 EIF3Deukaryotic translation initiation factor 3, subunit D 94 Hs.502244 EIF3Meukaryotic translation initiation factor 3, subunit M 95 Hs.467084EIF4G3 eukaryotic translation initiation factor 4 gamma, 3 96 Hs.433702EIF5 eukaryotic translation initiation factor 5 97 Hs.483494 ETF1eukaryotic translation termination factor 1 98 Hs.517293 F11R F11receptor 99 Hs.518662 FAM129A family with sequence similarity 129,member A 100 Hs.490795 FAM62B family with sequence similarity 62 (C2domain containing) member B 101 Hs.335918 FDPS farnesyl diphosphatesynthase (farnesyl pyrophosphate synthetase,dimethylallyltranstransferase, geranyltranstransferase) 102 Hs.86131FADD (includes Fas (TNFRSF6)-associated via death domain EG: 8772) 103Hs.408061 FABP5 fatty acid binding protein 5 (psoriasis-associated) 104Hs.433300 FCER1G Fc fragment of IgE, high affinity I, receptor for;gamma polypeptide 105 Hs.509343 FERMT2 fermitin family homolog 2(Drosophila) 106 Hs.338207 FRAP1 FK506 binding protein 12-rapamycinassociated protein 1 107 Hs.407190 FKBP5 FK506 binding protein 5 108Hs.409065 FEN1 flap structure-specific endonuclease 1 109 Hs.494496 FBP1fructose-1,6-bisphosphatase 1 110 Hs.654961 FUT8 fucosyltransferase 8(alpha (1,6) fucosyltransferase) 111 Hs.390567 FYN FYN oncogene relatedto SRC, FGR, YES 112 Hs.530024 GGCT gamma-glutamyl cyclotransferase 113Hs.27059 GMPPA GDP-mannose pyrophosphorylase A 114 Hs.567488 GMPPBGDP-mannose pyrophosphorylase B 115 Hs.591069 GBAS glioblastomaamplified sequence 116 Hs.654465 GCLC glutamate-cysteine ligase,catalytic subunit 117 Hs.390667 GSTK1 glutathione S-transferase kappa 1118 Hs.59138 GYPC glycophorin C (Gerbich blood group) 119 Hs.344151GOLGA4 golgi autoantigen, golgin subfamily a, 4 120 Hs.431317 GORASP2golgi reassembly stacking protein 2, 55 kDa 121 Hs.290243 GBF1golgi-specific brefeldin A resistant guanine nucleotide exchange factor1 122 Hs.485449 GTPBP2 GTP binding protein 2 123 Hs.495134 GAPVD1 GTPaseactivating protein and VPS9 domains 1 124 Hs.591450 GBP7 guanylatebinding protein 7 125 Hs.655196 HP haptoglobin 126 Hs.531785 HS1BP3HCLS1 binding protein 3 127 Hs.36927 HSPH1 heat shock 105 kDa/110 kDaprotein 1 128 Hs.690634 HSPA1L heat shock 70 kDa protein 1-like 129Hs.432648 HSPA2 heat shock 70 kDa protein 2 130 Hs.509736 HSP90AB1 heatshock protein 90 kDa alpha (cytosolic), class B member 1 131 Hs.525084HECTD3 HECT domain containing 3 132 Hs.642618 HEBP1 heme binding protein1 133 IPI00784636 HBB (includes hemoglobin, beta EG: 3043) 134 Hs.699280HBD hemoglobin, delta 135 Hs.502617 HNRNPCL1 heterogeneous nuclearribonucleoprotein C-like 1 136 Hs.69293 HEXB hexosaminidase B (betapolypeptide) 137 Hs.83634 HCFC1 host cell factor C1 (VP16-accessoryprotein) 138 Hs.460002 FLJ11151 hypothetical protein FLJ11151 139Hs.78880 ILVBL ilvB (bacterial acetolactate synthase)-like 140IPI00384938 IGHG1 immunoglobulin heavy constant gamma 1 (G1m marker) 141Hs.699240 IPO5 importin 5 142 Hs.434102 IKBKG inhibitor of kappa lightpolypeptide gene enhancer in B-cells, kinase gamma 143 Hs.500546 IDEinsulin-degrading enzyme 144 Hs.513225 ITFG3 integrin alpha FG-GAPrepeat containing 3 145 Hs.375957 ITGB2 integrin, beta 2 (complementcomponent 3 receptor 3 and 4 subunit) 146 Hs.431460 ICAM2 intercellularadhesion molecule 2 147 Hs.591110 IDH3A isocitrate dehydrogenase 3(NAD+) alpha 148 Hs.515247 JAK3 Janus kinase 3 (a protein tyrosinekinase, leukocyte) 149 Hs.301613 JTV1 JTV1 gene 150 Hs.527919 KPNA3karyopherin alpha 3 (importin alpha 4) 151 Hs.270043 KIAA0196 KIAA0196152 Hs.368255 KIAA0368 KIAA0368 153 Hs.368282 KIAA0564 KIAA0564 154IPI00396421 KIAA0776 KIAA0776 155 Hs.654497 LTBP1 latent transforminggrowth factor beta binding protein 1 156 Hs.478067 LXN latexin 157Hs.432674 LARS leucyl-tRNA synthetase 158 Hs.700163 LY6G5B lymphocyteantigen 6 complex, locus G5B 159 Hs.3100 KARS lysyl-tRNA synthetase 160Hs.654404 HLA-C major histocompatibility complex, class I, C 161Hs.75694 MPI mannose phosphate isomerase 162 Hs.696082 MAPKSP1 MAPKscaffold protein 1 163 Hs.444969 MEMO1 mediator of cell motility 1(includes EG: 51072) 164 Hs.486189 MAGI3 membrane associated guanylatekinase, WW and PDZ domain containing 3 165 Hs.500842 MGEA5 meningiomaexpressed antigen 5 (hyaluronidase) 166 Hs.377155 MTDH metadherin 167Hs.516157 MAT2A methionine adenosyltransferase II, alpha 168 Hs.252457MVD mevalonate (diphospho) decarboxylase 169 Hs.580782 MACF1microtubule-actin crosslinking factor 1 170 Hs.517949 MAP4microtubule-associated protein 4 171 Hs.515860 MAPRE3microtubule-associated protein, RP/EB family, member 3 172 Hs.269944MTCH2 mitochondrial carrier homolog 2 (C. elegans) 173 Hs.861 MAPK3mitogen-activated protein kinase 3 174 Hs.507681 MAP3K7IP1mitogen-activated protein kinase kinase kinase 7 interacting protein 1175 Hs.643565 MAPKAPK2 mitogen-activated protein kinase-activatedprotein kinase 2 176 Hs.591221 MYCBP2 MYC binding protein 2 177 Hs.91531MLLT6 myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog,Drosophila); translocated to, 6 178 Hs.655278 MYOF myoferlin 179Hs.286226 MYO1C myosin IC 180 IPI00719669 MRLC2 myosin regulatory lightchain MRLC2 181 IPI00007858 MYH13 myosin, heavy chain 13, skeletalmuscle 182 IPI00001753 MYH4 myosin, heavy chain 4, skeletal muscle 183Hs.463300 MYL4 myosin, light chain 4, alkali; atrial, embryonic 184Hs.926 MX2 myxovirus (influenza virus) resistance 2 (mouse) 185Hs.527412 ASAH1 N-acylsphingosine amidohydrolase (acid ceramidase) 1 186Hs.651219 NDUFA5 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 5,13 kDa 187 IPI00074489 NDUFB10 NADH dehydrogenase (ubiquinone) 1 betasubcomplex, 10, 22 kDa 188 Hs.532853 NDUFB7 NADH dehydrogenase(ubiquinone) 1 beta subcomplex, 7, 18 kDa 189 Hs.471207 NDUFS1 NADHdehydrogenase (ubiquinone) Fe—S protein 1, 75 kDa (NADH-coenzyme Qreductase) 190 Hs.90443 NDUFS8 NADH dehydrogenase (ubiquinone) Fe—Sprotein 8, 23 kDa (NADH-coenzyme Q reductase) 191 Hs.464572 NDUFV2 NADHdehydrogenase (ubiquinone) flavoprotein 2, 24 kDa 192 Hs.473937 NDUFV3NADH dehydrogenase (ubiquinone) flavoprotein 3, 10 kDa 193 Hs.655006NCKIPSD NCK interacting protein with SH3 domain 194 Hs.603732 NCKAP1NCK-associated protein 1 195 Hs.467759 NBAS neuroblastoma amplifiedsequence 196 Hs.524116 NRGN neurogranin (protein kinase C substrate,RC3) 197 Hs.587558 NCF2 neutrophil cytosolic factor 2 198 Hs.493164NAPRT1 nicotinate phosphoribosyltransferase domain containing 1 199Hs.696107 NEK9 (includes NIMA (never in mitosis gene a)-related kinase 9EG: 91754) 200 Hs.524082 NLRX1 NLR family member X1 201 Hs.532790 NMT1N-myristoyltransferase 1 202 Hs.319334 NASP nuclear autoantigenic spermprotein (histone-binding) 203 Hs.263812 NUDC nuclear distribution gene Chomolog (A. nidulans) 204 Hs.654408 NFKB1 nuclear factor of kappa lightpolypeptide gene enhancer in B-cells 1 205 Hs.325978 NUMA1 nuclearmitotic apparatus protein 1 206 Hs.79110 NCL nucleolin 207 Hs.643487NUP160 nucleoporin 160 kDa 208 Hs.555956 NUDT5 nudix (nucleosidediphosphate linked moiety X)-type motif 5 209 Hs.405410 OGT (includesO-linked N-acetylglucosamine (GlcNAc) transferase (UDP-N- EG: 8473)acetylglucosamine:polypeptide-N-acetylglucosaminyl transferase) 210Hs.695379 OPTN optineurin 211 Hs.430849 OSBPL8 oxysterol bindingprotein-like 8 212 Hs.656789 PAK3 p21 protein (Cdc42/Rac)-activatedkinase 3 213 Hs.98475 PNKD (includes paroxysmal nonkinesigenicdyskinesia EG: 25953) 214 Hs.495471 PMPCA peptidase (mitochondrialprocessing) alpha 215 Hs.33455 PADI2 peptidyl arginine deiminase, typeII 216 IPI00745933 PPIA (includes peptidylprolyl isomerase A(cyclophilin A) EG: 5478) 217 Hs.644938 PCYT2 phosphatecytidylyltransferase 2, ethanolamine 218 Hs.372295 PITPNM1phosphatidylinositol transfer protein, membrane-associated 1 219Hs.272759 PITPNM2 phosphatidylinositol transfer protein,membrane-associated 2 220 Hs.75812 PCK2 phosphoenolpyruvatecarboxykinase 2 (mitochondrial) 221 Hs.75160 PFKM phosphofructokinase,muscle 222 Hs.26612 PGM2L1 phosphoglucomutase 2-like 1 223 Hs.487296PHGDH phosphoglycerate dehydrogenase 224 IPI00786982 PGAM5phosphoglycerate mutase family member 5 225 Hs.409834 PHPT1phosphohistidine phosphatase 1 226 Hs.32942 PIK3CGphosphoinositide-3-kinase, catalytic, gamma polypeptide 227 Hs.591953PLCB3 phospholipase C, beta 3 (phosphatidylinositol-specific) 228Hs.413111 PLCG2 phospholipase C, gamma 2 (phosphatidylinositol-specific)229 Hs.517216 PEA15 phosphoprotein enriched in astrocytes 15 230Hs.675491 PLXNA4 plexin A4 231 Hs.632833 PLXNB3 plexin B3 232 Hs.348609PARP10 poly (ADP-ribose) polymerase family, member 10 233 Hs.482038PAIP1 poly(A) binding protein interacting protein 1 234 Hs.507910 PGRMC2progesterone receptor membrane component 2 235 Hs.567410 PSMD14proteasome (prosome, macropain) 26S subunit, non-ATPase, 14 236IPI00555590 PSMB2 proteasome (prosome, macropain) subunit, beta type, 2237 IPI00064328 PRMT5 protein arginine methyltransferase 5 238 Hs.498570PRKCQ protein kinase C, theta 239 Hs.631923 PRKAR2A protein kinase,cAMP-dependent, regulatory, type II, alpha 240 Hs.514323 PPP1R9B proteinphosphatase 1, regulatory (inhibitor) subunit 9B 241 Hs.400740 PPP2R4protein phosphatase 2A activator, regulatory subunit 4 242 Hs.584019PPP6C protein phosphatase 6, catalytic subunit 243 Hs.591549 PTPN18protein tyrosine phosphatase, non-receptor type 18 (brain-derived) 244Hs.439152 PCDH12 protocadherin 12 245 Hs.78524 PRUNE prune homolog(Drosophila) 246 Hs.41735 P2RX1 purinergic receptor P2X, ligand-gatedion channel, 1 247 Hs.284491 PDXK pyridoxal (pyridoxine, vitamin B6)kinase 248 Hs.370781 PDXDC1 pyridoxal-dependent decarboxylase domaincontaining 1 249 Hs.470633 PDK1 pyruvate dehydrogenase kinase, isozyme 1250 Hs.534770 PKM2 pyruvate kinase, muscle 251 Hs.321541 RAB11A RAB11A,member RAS oncogene family 252 Hs.406799 RAB18 RAB18, member RASoncogene family 253 Hs.369017 RAB2A RAB2A, member RAS oncogene family254 Hs.567328 RAB5B RAB5B, member RAS oncogene family 255 Hs.650382RAB5C RAB5C, member RAS oncogene family 256 Hs.591552 RAB6C RAB6C,member RAS oncogene family 257 Hs.644420 RAB8A RAB8A, member RASoncogene family 258 Hs.493867 RCSD1 RCSD domain containing 1 259Hs.461925 RPA1 replication protein A1, 70 kDa 260 Hs.645283 RTN4reticulon 4 261 Hs.368631 ARHGAP10 Rho GTPase activating protein 10 262Hs.531807 ARHGAP25 Rho GTPase activating protein 25 263 Hs.508738ARHGEF7 Rho guanine nucleotide exchange factor (GEF) 7 264 Hs.465761ARHGEF18 rho/rac guanine nucleotide exchange factor (GEF) 18 265Hs.73839 RNASE3 ribonuclease, RNase A family, 3 (eosinophil cationicprotein) 266 Hs.388664 RPL11 ribosomal protein L11 267 Hs.374588 RPL17ribosomal protein L17 268 Hs.337766 RPL18A ribosomal protein L18a 269IPI00741405 LOC391282 ribosomal protein L23a pseudogene 12 270 Hs.649475RPL24 ribosomal protein L24 271 Hs.652114 RPL28 ribosomal protein L28272 Hs.433701 RPL37A ribosomal protein L37a (includes EG: 6168) 273IPI00796861 LOC100130892 ribosomal protein L7 pseudogene 32 274Hs.546289 RPS12 ribosomal protein S12 (includes EG: 6206) 275 Hs.370504RPS15A ribosomal protein S15a 276 IPI00401105 RPS25 ribosomal proteinS25 277 IPI00397963 RPS27 ribosomal protein S27 278 Hs.282376 RPS4Y1ribosomal protein S4, Y-linked 1 279 Hs.367761 RPS4Y2 ribosomal proteinS4, Y-linked 2 280 Hs.408073 RPS6 ribosomal protein S6 281 IPI00413108RPSA (includes ribosomal protein SA EG: 3921) 282 Hs.553723 RNF123 ringfinger protein 123 (includes EG: 63891) 283 Hs.306769 RUFY1 RUN and FYVEdomain containing 1 284 Hs.272822 RUVBL1 RuvB-like 1 (E. coli) 285Hs.515846 RUVBL2 RuvB-like 2 (E. coli) 286 Hs.632438 SEC22B SEC22vesicle trafficking protein homolog B (S. cerevisiae) 287 Hs.654429SEC24C SEC24 family, member C (S. cerevisiae) (includes EG: 9632) 288IPI00643835 SELP selectin P (granule membrane protein 140 kDa, antigenCD62) 289 Hs.632460 SELENBP1 selenium binding protein 1 290 Hs.2837435-Sep septin 5 291 Hs.440932 9-Sep septin 9 292 Hs.435661 SPTLC2 serinepalmitoyltransferase, long chain base subunit 2 293 Hs.433343 SRRM2serine/arginine repetitive matrix 2 294 Hs.409578 STK38 serine/threoninekinase 38 295 IPI00168350 RP6-213H19.1 serine/threonine protein kinaseMST4 296 Hs.368077 SERPINB8 serpin peptidase inhibitor, clade B(ovalbumin), member 8 297 Hs.531176 SARS seryl-tRNA synthetase 298Hs.643526 SETDB1 SET domain, bifurcated 1 299 Hs.285666 SH3PXD2B SH3 andPX domains 2B 300 Hs.601143 SH3BP1 SH3-domain binding protein 1 301Hs.514495 SRP68 signal recognition particle 68 kDa 302 Hs.409223 SSR4signal sequence receptor, delta (translocon-associated protein delta)303 IPI00399212 LOC389842 similar to RanBP1 304 Hs.591680 SCYE1 smallinducible cytokine subfamily E, member 1 (endothelialmonocyte-activating) 305 Hs.356549 SNRPD3 small nuclearribonucleoprotein D3 polypeptide 18 kDa 306 Hs.632166 SNRPN smallnuclear ribonucleoprotein polypeptide N 307 Hs.83753 SNRPB small nuclearribonucleoprotein polypeptides B and B1 308 Hs.350927 SLC25A6 solutecarrier family 25 (mitochondrial carrier; adenine nucleotidetranslocator), member 6 309 Hs.656870 SLC25A24 solute carrier family 25(mitochondrial carrier; phosphate carrier), member 24 310 Hs.438723SLC27A3 solute carrier family 27 (fatty acid transporter), member 3 311Hs.656699 SLC27A4 solute carrier family 27 (fatty acid transporter),member 4 312 Hs.502769 SLC3A2 solute carrier family 3 (activators ofdibasic and neutral amino acid transport), member 2 313 Hs.469116 SLC9A1solute carrier family 9 (sodium/hydrogen exchanger), member 1 314 Hs.878SORD sorbitol dehydrogenase 315 Hs.505824 SAMM50 sorting and assemblymachinery component 50 homolog (S. cerevisiae) 316 Hs.32706 SPTBN4spectrin, beta, non-erythrocytic 4 317 Hs.558463 SPEN spen homolog,transcriptional regulator (Drosophila) 318 Hs.436306 SPHKAP SPHK1interactor, AKAP domain containing 319 Hs.406423 SF3B2 splicing factor3b, subunit 2, 145 kDa 320 Hs.679714 SFRS1 splicing factor,arginine/serine-rich 1 321 Hs.309090 SFRS7 splicing factor,arginine/serine-rich 7.35 kDa 322 Hs.591922 SLK STE20-like kinase(yeast) 323 Hs.3439 STOML2 stomatin (EPB72)-like 2 324 Hs.656726 STRNstriatin, calmodulin binding protein 325 Hs.440475 SDHA (includessuccinate dehydrogenase complex, subunit A, flavoprotein (Fp) EG: 6389)326 Hs.465924 SDHB (includes succinate dehydrogenase complex, subunit B,iron sulfur (Ip) EG: 6390) 327 Hs.494827 SUSD1 sushi domain containing 1328 Hs.83734 STX4 syntaxin 4 329 Hs.530436 STXBP3 syntaxin bindingprotein 3 330 Hs.643566 TAOK3 TAO kinase 3 331 IPI00642032 TXNL1thioredoxin-like 1 332 Hs.30345 TRAP1 TNF receptor-associated protein 1333 Hs.87968 TLR9 toll-like receptor 9 334 Hs.475733 TOP2B topoisomerase(DNA) II beta 180 kDa 335 Hs.496459 TOR1AIP1 torsin A interactingprotein 1 336 Hs.34024 TNIK TRAF2 and NCK interacting kinase 337Hs.529618 TFRC transferrin receptor (p90, CD71) 338 Hs.517033 TGM2transglutaminase 2 (C polypeptide,protein-glutamine-gamma-glutamyltransferase) 339 Hs.96247 TSNAXtranslin-associated factor X 340 Hs.654824 TM9SF2 transmembrane 9superfamily member 2 341 Hs.502 TAP2 transporter 2, ATP-bindingcassette, sub-family B (MDR/TAP) 342 IPI00018853 TPM1 tropomyosin 1(alpha) 343 Hs.535581 TPM3 tropomyosin 3 344 Hs.497599 WARStryptophanyl-tRNA synthetase 345 Hs.31053 TBCB tubulin folding cofactorB 346 Hs.279669 TUBG1 tubulin, gamma 1 347 Hs.473296 TPD52L2 tumorprotein D52-like 2 348 IPI00794254 YWHAH tyrosine3-monooxygenase/tryptophan 5-monooxygenase activation protein, etapolypeptide 349 Hs.9589 UBQLN1 ubiquilin 1 350 Hs.5308 UBA52 ubiquitinA-52 residue ribosomal protein fusion product 1 351 Hs.474213 UFD1Lubiquitin fusion degradation 1 like (yeast) 352 Hs.632370 UBE4Bubiquitination factor E4B (UFD2 homolog, yeast) 353 IPI00019932 UBE2D2ubiquitin-conjugating enzyme E2D 2 (UBC4/5 homolog, yeast) 354 Hs.50308UBE2K ubiquitin-conjugating enzyme E2K (UBC1 homolog, yeast) 355IPI00216316 UROS uroporphyrinogen III synthase 356 Hs.292689 USO1 USO1homolog, vesicle docking protein (yeast) 357 Hs.499925 VPS26A vacuolarprotein sorting 26 homolog A (S. pombe) 358 Hs.418175 VPS28 vacuolarprotein sorting 28 homolog (S. cerevisiae) 359 Hs.592009 VPS33A vacuolarprotein sorting 33 homolog A (S. cerevisiae) 360 Hs.631535 AKT2 v-aktmurine thymoma viral oncogene homolog 2 361 Hs.632066 VCPIP1 valosincontaining protein (p97)/p47 complex interacting protein 1 362 Hs.515469VASP vasodilator-stimulated phosphoprotein 363 Hs.66708 VAMP3vesicle-associated membrane protein 3 (cellubrevin) 364 Hs.505033 KRASv-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 365 Hs.699154 LYNv-yes-1 Yamaguchi sarcoma viral related oncogene homolog 366 Hs.635221WASF3 WAS protein family, member 3 367 Hs.356604 WNK1 WNK lysinedeficient protein kinase 1 368 Hs.390623 XPNPEP1 X-prolyl aminopeptidase(aminopeptidase P) 1, soluble 369 Hs.27239 ZDHHC5 zinc finger, DHHC-typecontaining 5 370 Hs.37003 Not Annotated Not Annotated 371 Hs.102696 NotAnnotated 372 Hs.10326 COPE 373 Hs.10649 C1orf38 374 Hs.108049 NotAnnotated Not Annotated 375 Hs.108957 Not Annotated Not Annotated 376Hs.111024 Not Annotated Not Annotated 377 Hs.115242 Not Annotated NotAnnotated 378 Hs.116237 Not Annotated Not Annotated 379 Hs.11638 ACSL5380 Hs.119825 Not Annotated Not Annotated 381 Hs.124027 Not AnnotatedNot Annotated 382 Hs.124126 Not Annotated Not Annotated 383 Hs.12865NSFL1C 384 Hs.131255 Not Annotated Not Annotated 385 Hs.131489 NotAnnotated Not Annotated 386 Hs.132499 Not Annotated Not Annotated 387Hs.132858 Not Annotated Not Annotated 388 Hs.133512 Not Annotated NotAnnotated 389 Hs.134688 Not Annotated Not Annotated 390 Hs.136309 NotAnnotated Not Annotated 391 Hs.138378 Not Annotated Not Annotated 392Hs.141125 Not Annotated Not Annotated 393 Hs.142003 Not Annotated NotAnnotated 394 Hs.1422 FGR 395 Hs.1437 GAA 396 Hs.143703 EHD4 397Hs.144011 CYTH2 398 Hs.144447 BRWD2 399 Hs.146406 DEDD 400 Hs.146602UQCRQ 401 Hs.149957 RPS6KA1 402 Hs.150206 HIST1H1A 403 Hs.150718 JAM3/// LOC100133502 404 Hs.152944 VWA5A 405 Hs.154078 LBP 406 Hs.155975PTPRCAP 407 Hs.158331 RENBP 408 Hs.15977 NDUFB9 409 Hs.161357 PDHB 410Hs.162121 COPA 411 Hs.16355 MYH10 412 Hs.163867 CD14 413 Hs.166011CTNND1 414 Hs.166551 FAM114A2 415 Hs.166924 SEC13 416 Hs.169284 PRPS1L1417 Hs.169900 PABPC4 418 Hs.171626 SKP1 419 Hs.173043 MTA2 420 Hs.17614ABCB10 421 Hs.179309 UBQLN2 422 Hs.18192 SRRM1 423 Hs.182625 VAPB 424Hs.1872 Not Annotated Not Annotated 425 Hs.188401 ANXA10 426 Hs.188882NUDT3 427 Hs.189075 TWF1 428 Hs.18925 CRBN 429 Hs.189409 FNBP1 430Hs.190086 MRCL3 431 Hs.191213 SNX9 432 Hs.194148 YES1 433 Hs.195080 ECE1434 Hs.196437 MOBKL1B 435 Hs.200804 SDCBP 436 Hs.204041 AHSA1 437Hs.2057 Not Annotated Not Annotated 438 Hs.211463 DNM2 439 Hs.21160 ME1440 Hs.212088 EPHX2 441 Hs.213389 GOLGB1 442 Hs.213470 PSMB7 443Hs.214142 MTHFR 444 Hs.220594 CCDC58 445 Hs.224171 ENO3 446 Hs.238839SCYL1 447 Hs.239818 PIK3CB 448 Hs.24956 INF2 449 Hs.271954 Not AnnotatedNot Annotated 450 Hs.296422 Not Annotated Not Annotated 451 Hs.3016581554440_at 1554440_at 452 Hs.328865 Not Annotated Not Annotated 453Hs.351544 Not Annotated Not Annotated 454 Hs.368359 Not Annotated NotAnnotated 455 Hs.370503 Not Annotated Not Annotated 456 Hs.37712AW006941 AW006941 457 Hs.43505 AF091453 458 Hs.435775 Not Annotated NotAnnotated 459 Hs.439474 Not Annotated Not Annotated 460 Hs.440534 NotAnnotated Not Annotated 461 Hs.460988 Not Annotated Not Annotated 462Hs.470544 Not Annotated Not Annotated 463 Hs.471528 Not Annotated NotAnnotated 464 Hs.486856 Not Annotated Not Annotated 465 Hs.500674 NotAnnotated Not Annotated 466 Hs.590925 Not Annotated Not Annotated 467Hs.591005 Not Annotated Not Annotated 468 Hs.591366 Not Annotated NotAnnotated 469 Hs.599301 Not Annotated Not Annotated 470 Hs.632735 NotAnnotated Not Annotated 471 Hs.637017 Not Annotated Not Annotated 472Hs.645248 Not Annotated Not Annotated 473 Hs.654497 Not Annotated NotAnnotated 474 Hs.659335 Not Annotated Not Annotated 475 Hs.694210 NotAnnotated Not Annotated 476 Hs.696132 Not Annotated Not Annotated 477Hs.699333 Not Annotated Not Annotated 478 Hs.699367 Not Annotated NotAnnotated 479 Hs.700648 Not Annotated Not Annotated 480 Hs.700676 NotAnnotated Not Annotated 481 Hs.700760 Not Annotated Not Annotated 482IPI00011791 Not Annotated Not Annotated 483 IPI00026138 Not AnnotatedNot Annotated 484 IPI00027007 Not Annotated Not Annotated 485IPI00061977 Not Annotated Not Annotated 486 IPI00140827 Not AnnotatedNot Annotated 487 IPI00152990 Not Annotated Not Annotated 488IPI00165486 Not Annotated 489 IPI00167258 Not Annotated 490 IPI00176593Not Annotated 491 IPI00176692 Not Annotated 492 IPI00176854 NotAnnotated 493 IPI00332493 Not Annotated 494 IPI00386403 Not Annotated495 IPI00397713 Not Annotated 496 IPI00397808 Not Annotated 497IPI00398435 Not Annotated 498 IPI00412216 Not Annotated 499 IPI00457006Not Annotated 500 IPI00478310 Not Annotated 501 IPI00556589 NotAnnotated 502 IPI00738024 Not Annotated 503 IPI00745518 Not Annotated504 IPI00746177 Not Annotated 505 IPI00788196 Not Annotated 506IPI00792850 Not Annotated 507 IPI00796208 Not Annotated 508 IPI00797737Not Annotated 509 IPI00807559 Not Annotated 510 IPI00807559 NotAnnotated

TABLE J Fold Change International (positive numbers Protein areupregulated Index/UniGene Symbol Entrez Gene Name in B1) 1 Hs.180946RPL5 (includes ribosomal protein L5 2.991594141 EG: 6125) 2 Hs.520026VARS valyl-tRNA synthetase 1.788666142 3 Hs.664670 Not Annotated1.863546477 4 IPI00001539 ACAA2 acetyl-Coenzyme A acyltransferase 21.778012617 5 Hs.631827 ANXA7 annexin A7 1.962977658 6 Hs.466044 PKN1protein kinase N1 2.926215231 7 Hs.90093 HSPA4 heat shock 70 kDa protein4 2.324540439 8 Hs.185172 GNB2 guanine nucleotide binding protein (Gprotein), beta polypeptide 2 2.321199972 9 IPI00003438 DNAJC8 DnaJ(Hsp40) homolog, subfamily C, member 8 3.049698528 10 Hs.431850 MAPK1mitogen-activated protein kinase 1 1.472676636 11 Hs.50382 TJP2 tightjunction protein 2 (zona occludens 2) 2.014271952 12 Hs.180414 NotAnnotated 1.683155132 13 Hs.186350 RPL4 ribosomal protein L4 2.71051803914 Hs.699250 B2M beta-2-microglobulin 2.103571916 15 Hs.591897 NotAnnotated 2.715551514 16 Hs.489284 ARPC1B actin related protein 2/3complex, subunit 1B, 41 kDa 2.034992123 17 Hs.514934 CAPZA1 cappingprotein (actin filament) muscle Z-line, alpha 1 2.337884511 18 Hs.431279NSF N-ethylmaleimide-sensitive factor 2.608040048 19 Hs.700570 APPamyloid beta (A4) precursor protein −2.395893698 20 Hs.279259 EPXeosinophil peroxidase 2.005473585 21 Hs.644618 SLC25A5 solute carrierfamily 25 (mitochondrial carrier; adenine nucleotide 2.377793261translocator), member 5 22 Hs.477155 ATP6V1A ATPase, H+ transporting,lysosomal 70 kDa, V1 subunit A 1.592166761 23 Hs.75318 TUBA4A tubulin,alpha 4a 1.410317852 24 Hs.184233 HSPA9 heat shock 70 kDa protein 9(mortalin) 3.890588764 25 Hs.521640 RAD23B RAD23 homolog B (S.cerevisiae) 1.945040444 26 Hs.370581 CAP1 CAP, adenylatecyclase-associated protein 1 (yeast) 2.08626543 27 Hs.522969 PADI4peptidyl arginine deiminase, type IV −2.585597629 28 Hs.483408 NotAnnotated 2.427608273 29 Hs.437594 RPLP2 ribosomal protein, large, P21.762376912 30 Hs.546285 RPLP0 (includes ribosomal protein, large, P02.401809197 EG: 6175) 31 Hs.300816 RAB1B (includes RAB1B, member RASoncogene family 2.036788097 EG: 81876) 32 Hs.632535 SSB (includesSjogren syndrome antigen B (autoantigen La) 1.848049688 EG: 6741) 33Hs.38449 SERPINE2 serpin peptidase inhibitor, clade E (nexin,plasminogen activator 1.839116473 inhibitor type 1), member 2 34Hs.374596 TPT1 (includes tumor protein, translationally-controlled 11.916065103 EG: 7178) 35 Hs.148559 IMMT inner membrane protein,mitochondrial (mitofilin) 2.208812239 36 Hs.405144 SFRS3 splicingfactor, arginine/serine-rich 3 1.854287873 37 Hs.274309 ERAF erythroidassociated factor −2.404141665 38 Hs.413812 RAC1 ras-related C3botulinum toxin substrate 1 (rho family, small GTP 3.007255119 bindingprotein Rac1) 39 Hs.25318 RAB27B RAB27B, member RAS oncogene family1.762079978 40 Hs.355934 SFPQ splicing factor proline/glutamine-rich(polypyrimidine tract binding 2.033693659 protein associated) 41Hs.464336 P4HB prolyl 4-hydroxylase, beta polypeptide 2.058272651 42Hs.247362 DDAH2 dimethylarginine dimethylaminohydrolase 2 2.191528732 43Hs.527105 HNRPDL heterogeneous nuclear ribonucleoprotein D-like3.323650054 44 Hs.502842 CAPN1 calpain 1, (mu/l) large subunit1.844181806 45 Hs.12970 PSMD3 proteasome (prosome, macropain) 26Ssubunit, non-ATPase, 3 1.509756576 46 IPI00011891 Not Annotated1.949391219 47 Hs.373763 HNRNPR heterogeneous nuclear ribonucleoproteinR 3.183271632 48 Hs.440898 FCN1 ficolin (collagen/fibrinogen domaincontaining) 1 −1.921894928 49 Hs.644646 KIF5B kinesin family member 5B−1.435375448 50 Hs.63348 EMILIN1 elastin microfibril interfacer 11.663039334 51 Hs.153837 MNDA myeloid cell nuclear differentiationantigen 1.689289277 52 Hs.656176 RBM4 RNA binding motif protein 41.899826892 53 Hs.77793 CSK c-src tyrosine kinase 1.724761961 54Hs.627414 RPS18 ribosomal protein S18 3.348251322 55 Hs.497788 EPRSglutamyl-prolyl-tRNA synthetase 1.466442524 56 Hs.698340 Not Annotated1.921786734 57 Hs.699298 CDV3 CDV3 homolog (mouse) 1.486895919 58Hs.111779 SPARC secreted protein, acidic, cysteine-rich (osteonectin)−2.780445145 59 IPI00011891 PRKAA1 protein kinase, AMP-activated, alpha1 catalytic subunit 2.713587735 60 Hs.495541 C9ORF167 chromosome 9 openreading frame 167 1.599094872 61 Hs.651923 CNN2 calponin 2 1.73178261462 Hs.131711 DLD dihydrolipoamide dehydrogenase 1.948923988 63 Hs.644809Not Annotated 2.338316865 64 Hs.643072 RAB10 RAB10, member RAS oncogenefamily 1.911187131 65 Hs.2853 PCBP1 (includes poly(rC) binding protein 11.878028726 EG: 5093) 66 Hs.19121 AP2A2 adaptor-related protein complex2, alpha 2 subunit 2.290995374 67 Hs.690198 CDC42 cell division cycle 42(GTP binding protein, 25 kDa) 2.382171241 68 Hs.271510 GSR glutathionereductase 2.161827645 69 Hs.524161 RSU1 Ras suppressor protein 11.436279998 70 Hs.406277 SF3A1 splicing factor 3a, subunit 1, 120 kDa3.35665152 71 Hs.558314 CP ceruloplasmin (ferroxidase) −4.832439476 72Hs.75514 NP (includes nucleoside phosphorylase 1.500961251 EG: 4860) 73Hs.501684 NAP1L4 nucleosome assembly protein 1-like 4 2.209825746 74Hs.571177 SYNCRIP synaptotagmin binding, cytoplasmic RNA interactingprotein 2.269580549 75 Hs.695941 HK1 hexokinase 1 1.893698231 76Hs.368149 CCT7 chaperonin containing TCP1, subunit 7 (eta) 1.43390681477 Hs.695925 DUSP3 dual specificity phosphatase 3 2.286782204 78Hs.75066 TSN translin −2.048787544 79 Hs.474751 MYH9 myosin, heavy chain9, non-muscle 2.033216171 80 Hs.644809 Not Annotated 3.013475764 81Hs.655207 F2 coagulation factor II (thrombin) −2.861439244 82 Hs.143436PLG plasminogen −1.893142835 83 Hs.420529 UBE2V1 ubiquitin-conjugatingenzyme E2 variant 1 3.119742802 84 Hs.190028 GSTO1 glutathioneS-transferase omega 1 1.353315555 85 Hs.20107 KLC1 kinesin light chain 11.756378314 86 Hs.626404 RAB11B RAB11B, member RAS oncogene family1.540804975 87 Hs.460109 MYH11 myosin, heavy chain 11, smooth muscle2.332116359 88 Hs.490415 ZYX zyxin 2.38059363 89 Hs.138860 ARHGAP1 RhoGTPase activating protein 1 1.851916091 90 Hs.646283 VISA virus-inducedsignaling adapter 1.446706533 91 Hs.8004 KALRN kalirin, RhoGEF kinase4.58940432 92 Hs.594673 Not Annotated 1.559917838 93 Hs.707 KRT2 keratin2 2.661810703 94 Hs.699367 Not Annotated 1.552098437 95 Hs.280342PRKAR1A protein kinase, cAMP-dependent, regulatory, type I, alpha(tissue 1.634710854 specific extinguisher 1) 96 Hs.73849 APOC3apolipoprotein C-III 3.025507594 97 Hs.546255 FGG fibrinogen gamma chain2.194270748 98 Hs.75307 H1FX H1 histone family, member X 2.411319459 99Hs.632729 FAM62A family with sequence similarity 62 (C2 domaincontaining), member A 1.737053335 100 Hs.120759 APOB apolipoprotein B(including Ag(x) antigen) −3.022308409 101 Hs.72933 PF4V1 plateletfactor 4 variant 1 −1.667015899 102 Hs.507866 C130RF15 chromosome 13open reading frame 15 2.508431485 103 Hs.203717 FN1 fibronectin 1−2.170422372 104 Hs.324746 AHSG alpha-2-HS-glycoprotein −4.302298793 105Hs.200770 SKAP2 src kinase associated phosphoprotein 2 1.755472125 106Hs.30054 F5 coagulation factor V (proaccelerin, labile factor)−1.567648564 107 Hs.372208 HSPC159 galectin-related protein 1.824854702108 Hs.505735 NACA nascent polypeptide-associated complex alpha subunit1.652441243 109 Hs.491351 CLTC clathrin, heavy chain (Hc) 1.743502579110 Hs.480042 ANXA3 annexin A3 −3.143396399 111 Hs.509226 FKBP3 FK506binding protein 3, 25 kDa 2.142363841 112 Hs.24258 GUCY1A3 guanylatecyclase 1, soluble, alpha 3 1.848134452 113 Hs.81934 ACADSBacyl-Coenzyme A dehydrogenase, short/branched chain 1.352453174 114Hs.429608 REEP5 receptor accessory protein 5 −1.629165972 115 Hs.75841ERP29 endoplasmic reticulum protein 29 2.32777609 116 Hs.413482 C210RF33chromosome 21 open reading frame 33 −1.338275818 117 Hs.502823 PRDX5peroxiredoxin 5 1.612032187 118 Hs.523302 PRDX3 peroxiredoxin 31.609936792 119 Hs.408054 RPL12 (includes ribosomal protein L122.804663051 EG: 6136) 120 IPI00024989 PCMT1 protein-L-isoaspartate(D-aspartate) O-methyltransferase 1.567802876 121 Hs.591095 PDIA3protein disulfide isomerase family A, member 3 1.780599508 122 Hs.430606CS citrate synthase −2.357926195 123 Hs.520973 HSPB1 heat shock 27 kDaprotein 1 1.923931973 124 Hs.518244 RPN1 ribophorin I 2.112462414 125Hs.695918 CAPZA2 capping protein (actin filament) muscle Z-line, alpha 22.146454384 126 Hs.632828 HNRNPH2 heterogeneous nuclearribonucleoprotein H2 (H′) 1.609307106 127 Hs.430425 GNB1 guaninenucleotide binding protein (G protein), beta polypeptide 1 1.915685862128 Hs.469473 RPL31 ribosomal protein L31 1.971237465 129 Hs.381072 PPIFpeptidylprolyl isomerase F 1.919712344 130 Hs.83190 FASN fatty acidsynthase 1.596744982 131 Hs.356624 NID1 nidogen 1 −1.567370157 132Hs.12084 TUFM Tu translation elongation factor, mitochondrial1.443666367 133 Hs.95990 PKLR pyruvate kinase, liver and RBC 2.624429792134 Hs.489040 SRI sorcin −1.668251058 135 Hs.192374 HSP90B1 heat shockprotein 90 kDa beta (Grp94), member 1 1.227206967 136 Hs.516155 CAPGcapping protein (actin filament), gelsolin-like 1.935086978 137 Hs.928PRTN3 proteinase 3 −2.191302631 138 Hs.179986 FLOT1 flotillin 12.62551323 139 Hs.315137 AARS alanyl-tRNA synthetase 2.138071963 140Hs.275243 S100A6 S100 calcium binding protein A6 −2.091908363 141Hs.656274 TNFAIP8 tumor necrosis factor, alpha-induced protein 81.848699684 142 Hs.654559 HNRNPL heterogeneous nuclear ribonucleoproteinL 2.064236514 143 Hs.471441 PSMB2 proteasome (prosome, macropain)subunit, beta type, 2 3.189407689 144 Hs.594095 Not Annotated1.541410846 145 Hs.7744 NDUFV1 NADH dehydrogenase (ubiquinone)flavoprotein 1, 51 kDa 1.859664494 146 Hs.517670 TTLL12 tubulin tyrosineligase-like family, member 12 1.548669753 147 Hs.159494 BTK Brutonagammaglobulinemia tyrosine kinase 1.744461371 148 Hs.153961 ACTR1A ARP1actin-related protein 1 homolog A, centractin alpha (yeast) 1.602174673149 Hs.98791 ACTR1B (includes ARP1 actin-related protein 1 homolog B,centractin beta (yeast) 2.447561282 EG: 10120) 150 IPI00029625 FLOT2flotillin 2 2.779048389 151 Hs.232375 ACAT1 acetyl-Coenzyme Aacetyltransferase 1 1.844709235 152 Hs.529451 DIAPH1 diaphanous homolog1 (Drosophila) 1.472455435 153 Hs.477352 PDIA5 protein disulfideisomerase family A, member 5 2.417726204 154 Hs.516032 HADHAhydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl-Coenzyme A 2.919893077thiolase/enoyl-Coenzyme A hydratase (trifunctional protein), alphasubunit 155 Hs.528007 U2AF2 (includes U2 small nuclear RNA auxiliaryfactor 2 2.33690845 EG: 11338) 156 Hs.655340 Not Annotated 1.994399205157 Hs.546303 Not Annotated 1.993258019 158 Hs.191346 7-Sep septin 71.426720758 159 Hs.556296 Not Annotated 1.918157196 160 Hs.546407 CAND1cullin-associated and neddylation-dissociated 1 1.355594109 161Hs.122523 SND1 staphylococcal nuclease and tudor domain containing 11.764952427 162 Hs.327252 Not Annotated 1.853845796 163 IPI00154742 IGL@immunoglobulin lambda locus −2.322679589 164 Hs.514412 PECAM1platelet/endothelial cell adhesion molecule 1.521872894 165 Hs.248267MPST mercaptopyruvate sulfurtransferase 1.802723925 166 Hs.436186 CASTcalpastatin 1.877444004 167 Hs.390567 FYN FYN oncogene related to SRC,FGR, YES 1.721126996 168 IPI00168728 IGHM immunoglobulin heavy constantmu −1.882125059 169 Hs.558799 PSMA3 proteasome (prosome, macropain)subunit, alpha type, 3 2.424171315 170 Hs.465808 HNRNPM heterogeneousnuclear ribonucleoprotein M 1.745065443 171 Hs.149185 CNDP2 CNDPdipeptidase 2 (metallopeptidase M20 family) 1.639294303 172 IPI00179291XPNPEP1 X-prolyl aminopeptidase (aminopeptidase P) 1, soluble1.443429746 173 Hs.555895 TMSL3 thymosin-like 3 −2.986973706 174Hs.126550 VPS4B vacuolar protein sorting 4 homolog B (S. cerevisiae)1.5707885 175 Hs.654720 KIAA1967 KIAA1967 3.861735646 176 Hs.49582PPP1R12A protein phosphatase 1, regulatory (inhibitor) subunit 12A−1.985284505 177 Hs.63489 PTPN6 protein tyrosine phosphatase,non-receptor type 6 2.403072934 178 Hs.535581 TPM3 tropomyosin 3−1.265339887 179 Hs.496984 MPP1 membrane protein, palmitoylated 1, 55kDa 1.825563177 180 Hs.515517 RPL18 ribosomal protein L18 3.659413318181 Hs.438429 RPS19 ribosomal protein S19 2.504016487 182 Hs.73722 APEX1APEX nuclease (multifunctional DNA repair enzyme) 1 2.126641285 183Hs.461047 G6PD glucose-6-phosphate dehydrogenase 1.330805366 184Hs.128548 WDR1 WD repeat domain 1 5.196770912 185 Hs.519320 VDAC1voltage-dependent anion channel 1 2.440307464 186 Hs.512675 RPS8ribosomal protein S8 2.401417871 187 Hs.494691 PFN1 profilin 11.824342002 188 Hs.180535 FERMT3 fermitin family homolog 3 (Drosophila)1.933107142 189 Hs.417303 SPTB spectrin, beta, erythrocytic 2.124657924190 Hs.446628 Not Annotated 2.082461305 191 Hs.1869 PGM1phosphoglucomutase 1 1.62661576 192 Hs.89497 LMNB1 lamin B1 1.892879233193 Hs.652308 MTHFD1 methylenetetrahydrofolate dehydrogenase (NADP+dependent) 1, 1.965807135 methenyltetrahydrofolate cyclohydrolase,formyltetrahydrofolate synthetase 194 Hs.446149 LDHB lactatedehydrogenase B 1.507117812 195 Hs.87752 MSN moesin 1.792183522 196Hs.253903 STOM stomatin 1.663466237 197 Hs.523836 GSTP1 glutathioneS-transferase pi 1 3.12010713 198 Hs.573688 PRDX6 peroxiredoxin 61.768671919 199 Hs.80828 KRT1 keratin 1 2.488668295 200 Hs.289123 DCTN2dynactin 2 (p50) 1.517636012 201 Hs.654554 Not Annotated −3.221258193202 Hs.90061 PGRMC1 progesterone receptor membrane component 11.645197721 203 Hs.514819 AP2B1 adaptor-related protein complex 2, beta1 subunit 1.967752606 204 Hs.467284 RPS9 ribosomal protein S92.046621121 205 Hs.397609 RPS16 ribosomal protein S16 3.411967491 206Hs.433427 RPS17 (includes ribosomal protein S17 3.95408013 EG: 6218) 207Hs.350899 CAPN2 calpain 2, (m/II) large subunit 1.680232488 208Hs.363137 TCP1 t-complex 1 1.787923894 209 Hs.520967 MDH2 malatedehydrogenase 2, NAD (mitochondrial) 1.559612551 210 Hs.699180 VCLvinculin 3.129938695 211 Hs.371563 RAB14 RAB14, member RAS oncogenefamily 2.101732978 212 Hs.83722 EPS15 epidermal growth factor receptorpathway substrate 15 1.373102908 213 Hs.277035 MGLL monoglyceride lipase1.805879512 214 Hs.64016 PROS1 protein S (alpha) −2.623015853 215Hs.584790 PPP2R1B protein phosphatase 2 (formerly 2A), regulatorysubunit A, beta −1.810743224 isoform 216 Hs.580681 SAMHD1 SAM domain andHD domain 1 2.000782596 217 Hs.444770 SH3KBP1 SH3-domain kinase bindingprotein 1 2.069800255 218 Hs.88778 CBR1 carbonyl reductase 1 1.904274616219 Hs.339278 COPB1 coatomer protein complex, subunit beta 1 1.443967836220 Hs.592490 FH fumarate hydratase 2.186123666 221 Hs.486458 ARHGAP18Rho GTPase activating protein 18 2.274383381 222 Hs.335513 F13A1coagulation factor XIII, A1 polypeptide 2.145284002 223 Hs.189772 CCT2chaperonin containing TCP1, subunit 2 (beta) 1.435139731 224 Hs.539684EIF2S3 eukaryotic translation initiation factor 2, subunit 3 gamma, 52kDa 2.261012155 225 Hs.33642 ARCN1 archain 1 2.07225933 226 Hs.370770XPO1 exportin 1 (CRM1 homolog, yeast) 2.343773987 227 Hs.573018 NotAnnotated 1.456482565 228 Hs.291030 IQGAP2 IQ motif containing GTPaseactivating protein 2 1.646289191 229 Hs.212102 PDIA6 protein disulfideisomerase family A, member 6 2.480879671 230 Hs.499839 RPL7A ribosomalprotein L7a 1.726750017 231 Hs.465041 HDHD2 haloacid dehalogenase-likehydrolase domain containing 2 2.231113926 232 Hs.654957 PPA2pyrophosphatase (inorganic) 2 2.076884027 233 Hs.660070 Not Annotated2.0488303 234 Hs.125113 CCT8 chaperonin containing TCP1, subunit 8(theta) 2.39782042 235 Hs.274402 HSPA1A heat shock 70 kDa protein 1A2.358211938 236 Hs.75285 ITIH2 inter-alpha (globulin) inhibitor H2−2.825741915 237 Hs.571886 AKR7A2 aldo-keto reductase family 7, memberA2 (aflatoxin aldehyde 2.166498126 reductase) 238 Hs.368794 AP1B1adaptor-related protein complex 1, beta 1 subunit 1.872459483 239Hs.599481 EIF4A2 eukaryotic translation initiation factor 4A, isoform 23.551326775 240 Hs.416848 CTSW cathepsin W −1.696934761 241 Hs.528668RPL6 ribosomal protein L6 2.430141179 242 Hs.368084 LRPPRC leucine-richPPR-motif containing −2.370581231 243 Hs.509736 HSP90AB1 heat shockprotein 90 kDa alpha (cytosolic), class B member 1 2.408626383 244Hs.632717 MYL6 myosin, light chain 6, alkali, smooth muscle andnon-muscle 3.625359469 245 Hs.654614 HSPA6 heat shock 70 kDa protein 6(HSP70B′) 2.880497988 246 Hs.567380 FUBP1 far upstream element (FUSE)binding protein 1 2.457237888 247 Hs.525600 HSP90AA1 heat shock protein90 kDa alpha (cytosolic), class A member 1 2.30575168 248 Hs.699168TUBA1B tubulin, alpha 1b 1.343588946 249 IPI00398135 Not Annotated1.706927145 250 Hs.128420 VPS4A vacuolar protein sorting 4 homolog A (S.cerevisiae) 2.041670779 251 Hs.591054 BID BH3 interacting domain deathagonist 1.977789146 252 Hs.200716 MECP2 methyl CpG binding protein 2(Rett syndrome) 2.115913201 253 Hs.155247 ALDOC aldolase C,fructose-bisphosphate 2.390316052 254 Hs.570791 LAP3 leucineaminopeptidase 3 1.7773007 255 Hs.598115 PPIA (includes peptidylprolylisomerase A (cyclophilin A) −1.252231897 EG: 5478) 256 Hs.356572 RPS3Aribosomal protein S3A 3.364033062 257 Hs.518530 PAK2 p21 protein(Cdc42/Rac)-activated kinase 2 1.820573252 258 Hs.98510 WDR44 WD repeatdomain 44 1.715515466 259 IPI00448925 IGHG1 immunoglobulin heavyconstant gamma 1 (G1m marker) −2.709398355 260 Hs.41045 UNC13D unc-13homolog D (C. elegans) 1.475081587 261 Hs.380956 Not Annotated2.840678067 262 Hs.404321 GARS glycyl-tRNA synthetase 2.140952373 263Hs.306769 RUFY1 RUN and FYVE domain containing 1 2.531625079 264Hs.292493 XRCC6 X-ray repair complementing defective repair in Chinesehamster cells 6 1.787163446 265 Hs.595053 HSPD1 heat shock 60 kDaprotein 1 (chaperonin) 1.255650787 266 Hs.699280 HBD hemoglobin, delta−2.913740187 267 Hs.655361 HPR (includes haptoglobin-related protein−4.710560337 EG: 3250) 268 Hs.534770 PKM2 pyruvate kinase, muscle1.537311441 269 Hs.2533 ALDH9A1 aldehyde dehydrogenase 9 family, memberA1 2.429592013 270 Hs.530687 RNH1 ribonuclease/angiogenin inhibitor 11.905230817 271 Hs.517168 TAGLN2 transgelin 2 1.822335623 272 Hs.14770BIN2 bridging integrator 2 1.68853164 273 Hs.436439 TWF2 twinfilin,actin-binding protein, homolog 2 (Drosophila) 1.884510405 274 Hs.433068PRKAR2B protein kinase, cAMP-dependent, regulatory, type II, beta1.54914478 275 Hs.502756 AHNAK AHNAK nucleoprotein 2.893577011 276Hs.515876 NRBP1 nuclear receptor binding protein 1 2.746197889 277Hs.132858 RAP1GDS1 RAP1, GTP-GDP dissociation stimulator 1 2.107982605279 Hs.311609 DDX39 DEAD (Asp-Glu-Ala-Asp) box polypeptide 39 2.84761005280 Hs.438678 TALDO1 transaldolase 1 2.691818999 282 IPI00746976 DNM1Ldynamin 1-like 1.617915807 283 Hs.270428 SUCLG1 succinate-CoA ligase,alpha subunit 2.37225264 284 Hs.471014 TLN1 talin 1 2.579118784

TABLE 2 Protein Transcript Matches of 393 mild CAN consensus genes ProbeSet ID UniGene ID Gene Title Gene Symbol 1 212224_at Hs.76392 aldehydedehydrogenase 1 family, member A1 ALDH1A1 2 209970_x_at Hs.2490 caspase1, apoptosis-related cysteine peptidase (interleukin 1, beta, CASP1convertase) 3 216799_at Hs.24907 Coronin, actin binding protein, 2BCORO2B 4 202902_s_at Hs.181301 cathepsin S CTSS 5 203276_at Hs.89497lamin B1 LMNB1 6 1559052_s_at Hs.518530 p21 (CDKN1A)-activated kinase 2PAK2 7 202803_s_at Hs.375957 integrin, beta 2 (antigen CD18 (p95),lymphocyte function-associated antigen ITGB2 1; macrophage antigen 1(mac-1) beta subunit) 8 224511_s_at Hs.408236 thioredoxin-like 5 ///thioredoxin-like 5 TXNL5 9 216063_at Hs.20205 hemoglobin, betapseudogene 1 /// hemoglobin, beta pseudogene 1 HBBP1 10 202277_atHs.90458 serine palmitoyltransferase, long chain base subunit 1 SPTLC1

TABLE 3 Protein Transcript Matches of 1066 mild CAN Data Set 1 genesProbe Set ID UniGene ID Gene Title Gene Symbol 1 212224_at Hs.76392aldehyde dehydrogenase 1 family, member A1 ALDH1A1 2 201089_at Hs.295917ATPase, H+ transporting, lysosomal 56/58 kDa, V1 subunit B, isoform 2ATP6V1B2 3 213312_at Hs.70769 chromosome 6 open reading frame 162C6orf162 4 206011_at Hs.2490 caspase 1, apoptosis-related cysteinepeptidase (interleukin 1, beta, CASP1 convertase) 5 202902_s_atHs.181301 cathepsin S CTSS 6 204714_s_at Hs.30054 coagulation factor V(proaccelerin, labile factor) F5 7 202957_at Hs.14601 Hematopoieticcell-specific Lyn substrate 1 HCLS1 8 205936_s_at Hs.411695 hexokinase 3(white cell) HK3 9 204959_at Hs.153837 myeloid cell nucleardifferentiation antigen /// myeloid cell nuclear MNDA differentiationantigen 10 208875_s_at Hs.518530 p21 (CDKN1A)-activated kinase 2 PAK2 11207668_x_at Hs.212102 protein disulfide isomerase family A, member 6PDIA6 12 227516_at Hs.406277 splicing factor 3a, subunit 1, 120 kDaSF3A1 13 217995_at Hs.511251 sulfide quinone reductase-like (yeast)SQRDL 14 220966_x_at Hs.132499 actin related protein 2/3 complex,subunit 5-like /// actin related protein 2/3 ARPC5L complex, subunit5-like 15 219505_at Hs.170310 cat eye syndrome chromosome region,candidate 1 CECR1 16 202295_s_at Hs.148641 cathepsin H CTSH 17209759_s_at Hs.403436 dodecenoyl-Coenzyme A delta isomerase (3,2trans-enoyl-Coenzyme A DCI isomerase) 18 204646_at Hs.335034dihydropyrimidine dehydrogenase DPYD 19 218610_s_at Hs.460002hypothetical protein FLJ11151 FLJ11151 20 209876_at Hs.434996 Gprotein-coupled receptor kinase interactor 2 GIT2 21 201944_at Hs.69293hexosaminidase B (beta polypeptide) HEXB 22 211023_at Hs.161357 pyruvatedehydrogenase (lipoamide) beta PDHB 23 202671_s_at Hs.284491 pyridoxal(pyridoxine, vitamin B6) kinase PDXK 24 225214_at Hs.213470 Proteasome(prosome, macropain) subunit, beta type, 7 PSMB7 25 217983_s_atHs.529989 ribonuclease T2 RNASET2 26 206034_at Hs.368077 serpinpeptidase inhibitor, clade B (ovalbumin), member 8 SERPINB8 27 204981_atHs.50868 solute carrier family 22 (organic cation transporter), member18 SLC22A18 28 219403_s_at Hs.44227 heparanase HPSE 29 232359_atHs.226007 Retinol dehydrogenase 11 (all-trans and 9-cis) RDH11 30203485_at Hs.368626 reticulon 1 RTN1 31 221532_s_at Hs.513055 WD repeatdomain 61 WDR61 32 208857_s_at Hs.279257 protein-L-isoaspartate(D-aspartate) O-methyltransferase PCMT1

TABLE 4 Protein Transcript Matches of 1429 mild CAN Data Set 2 genesProbe Set ID UniGene ID Gene Title Gene Symbol 1 201305_x_at Hs.494604acidic (leucine-rich) nuclear phosphoprotein 32 family, member B ANP32B2 216123_x_at Hs.514934 Capping protein (actin filament) muscle Z-line,alpha 1 CAPZA1 3 209970_x_at Hs.2490 caspase 1, apoptosis-relatedcysteine peptidase (interleukin 1, beta, CASP1 convertase) 4 209789_atHs.24907 coronin, actin binding protein, 2B CORO2B 5 237104_at Hs.181301Cathepsin S CTSS 6 202428_x_at Hs.78888 diazepam binding inhibitor (GABAreceptor modulator, acyl-Coenzyme A DBI binding protein) 7 235999_atHs.480073 Heterogeneous nuclear ribonucleoprotein D (AU-rich element RNAbinding HNRPD protein 1, 37 kDa) 8 243593_s_at Hs.465808 Heterogeneousnuclear ribonucleoprotein M HNRPM 9 201841_s_at Hs.520973 heat shock 27kDa protein 1 HSPB1 10 1566785_x_at Hs.431279 Ribosomal protein S7 NSF11 216253_s_at Hs.475074 parvin, beta PARVB 12 215628_x_at Hs.483408Protein phosphatase 2 (formerly 2A), catalytic subunit, alpha isoformPPP2CA 13 200927_s_at Hs.371563 RAB14, member RAS oncogene family RAB1414 213941_x_at Hs.546287 ribosomal protein S7 RPS7 15 240855_atHs.417303 Spectrin, beta, erythrocytic (includes spherocytosis, clinicaltype I) SPTB 16 237875_at Hs.519756 Serine/threonine kinase 10 STK10 17238749_at Hs.258314 Brain and reproductive organ-expressed (TNFRSF1Amodulator) BRE 18 1565868_at Hs.502328 CD44 antigen (homing function andIndian blood group system) CD44 18 1565868_at Hs.502328 CD44 antigen(homing function and Indian blood group system) CD44 19 226875_atHs.368203 dedicator of cytokinesis 11 DOCK11 20 208000_at Hs.86161 GPIanchored molecule like protein GML 21 243147_x_at Hs.432674 Leucyl-tRNAsynthetase LARS 22 226253_at Hs.143774 leucine rich repeat containing 45LRRC45 23 229851_s_at Hs.8360 PTD012 protein PTD012 24 208720_s_atHs.282901 RNA-binding region (RNP1, RRM) containing 2 RNPC2 25201742_x_at Hs.68714 splicing factor, arginine/serine-rich 1 (splicingfactor 2, alternate splicing SFRS1 factor) 26 215274_at Hs.369271 solutecarrier family 12 (sodium/chloride transporters), member 3 SLC12A3 27231324_at Hs.534350 SWI/SNF related, matrix associated, actin dependentregulator of chromatin, SMARCB1 subfamily b, member 1 28 215416_s_atHs.3439 stomatin (EPB72)-like 2 STOML2 29 206116_s_at Hs.133892tropomyosin 1 (alpha) TPM1 30 224511_s_at Hs.408236 thioredoxin-like 5/// thioredoxin-like 5 TXNL5 31 201266_at Hs.337766 thioredoxinreductase 1 TXNRD1 32 243160_at Hs.363396 Complement factor H CFH 33218218_at Hs.506603 DIP13 beta DIP13B 34 221942_s_at Hs.24258 guanylatecyclase 1, soluble, alpha 3 GUCY1A3 35 232169_x_at Hs.90443 NADHdehydrogenase (ubiquinone) Fe—S protein 8, 23 kDa (NADH-coenzyme QNDUFS8 reductase) 36 205190_at Hs.203637 plastin 1 (l isoform) PLS1 37202429_s_at Hs.435512 protein phosphatase 3 (formerly 2B), catalyticsubunit, alpha isoform PPP3CA (calcineurin A alpha) 38 1555340_x_atHs.190334 RAP1A, member of RAS oncogene family RAP1A 39 1569073_x_atHs.327527 SWI/SNF related, matrix associated, actin dependent regulatorof chromatin, SMARCA4 subfamily a, member 4 40 212577_at Hs.8118structural maintenance of chromosomes flexible hinge domain containing 1SMCHD1

TABLE 5 Protein Transcript Matches of 545 moderate/severe CAN Data Set 1genes Probe Set ID UniGene ID Gene Title Gene Symbol 1 223598_atHs.521640 RAD23 homolog B (S. cerevisiae) RAD23B 2 208000_at Hs.86161GPI anchored molecule like protein GML 3 1557724_a_at Hs.407190hypothetical protein LOC285847 LOC285847 4 236356_at Hs.471207 NADHdehydrogenase (ubiquinone) Fe—S protein 1, 75 kDa (NADH-coenzyme QNDUFS1 reductase) 5 238688_at Hs.133892 Tropomyosin 1 (alpha) TPM1 6218090_s_at Hs.144447 bromodomain and WD repeat domain containing 2BRWD2 7 200898_s_at Hs.500842 meningioma expressed antigen 5(hyaluronidase) MGEA5 8 201569_s_at Hs.505824 sorting and assemblymachinery component 50 homolog (S. cerevisiae) SAMM50 9 1560854_s_atHs.50216 zinc finger protein 588 ZNF588

TABLE 6 Protein Transcript Matches of 172 moderate/severe CAN Data Set 2genes Probe Set ID UniGene ID Gene Title Gene Symbol 1 216251_s_atHs.517670 KIAA0153 protein KIAA0153 2 204959_at Hs.153837 myeloid cellnuclear differentiation antigen /// myeloid cell nuclear MNDAdifferentiation antigen 3 227770_at Hs.128420 Vacuolar protein sorting4A (yeast) VPS4A 4 231324_at Hs.534350 SWI/SNF related, matrixassociated, actin dependent regulator of chromatin, SMARCB1 subfamily b,member 1 5 209029_at Hs.530823 COP9 constitutive photomorphogenichomolog subunit 7A (Arabidopsis) COPS7A 6 218326_s_at Hs.502176leucine-rich repeat-containing G protein-coupled receptor 4 LGR4 71568619_s_at Hs.530899 Hypothetical protein LOC162073 LOC162073 8204994_at Hs.926 myxovirus (influenza virus) resistance 2 (mouse) MX2 9205325_at Hs.334688 phytanoyl-CoA hydroxylase interacting protein PHYHIP

What is claimed is:
 1. A method of prognosing, diagnosing or monitoringCAN/IFTA (chronic allograft nephropathy, interstitial fibrosis andtubular atrophy, or chronic allograft nephropathy and interstitialfibrosis and tubular atrophy), comprising (a) obtaining target nucleicacids, wherein the target nucleic acids comprise mRNA from a bloodsample from a human subject or nucleic acids derived from the mRNA fromthe blood sample from the human subject, wherein the human subject is arecipient of a transplanted kidney and has received an immunosuppressantdrug; (b) contacting the target nucleic acids with at least ten probes,wherein the at least ten probes are specific for genes associated withthe presence or absence of CAN/IFTA and are specific for at least genesANTXR2, SYNPO, VSIG4, GFI1B, SPTLC2, RNF175, and EST56; (c) detectingexpression levels in the human subject of the at least genes ANTXR2,SYNPO, VSIG4, GFI1B, SPTLC2, RNF175, and EST56; (d) prognosing,diagnosing or monitoring CAN/IFTA in the transplanted kidney of thehuman subject when the expression levels of SYNPO and GFI1B detected instep (c) have a statistically significant negative-fold change relativeto a kidney transplant patient without CAN/IFTA and the expressionlevels of ANXR2, VSIG4, SPTLC2, RNF17S, and EST56 detected in step (c)have a statistically significant positive-fold change relative to akidney transplant patient without CAN/IFTA; and (e) administering anincreased dose of the immunosuppressant drug to the human subject inorder to treat or prevent the CAN/IFTA prognosed, diagnosed or monitoredin the transplanted kidney of the human subject in step (d) oradministering a new immunosuppressant drug to the human subject in orderto treat or prevent the CAN/IFTA prognosed, diagnosed or monitored inthe transplanted kidney of the human subject in step (d).
 2. The methodof claim 1, wherein step (c) further comprises for each of the at leastgenes ANTXR2, SYNPO, VSIG4, GFI1B, SPTLC2, RNF175, and EST56 assigningthe expression level of the gene in the human subject a value or otherdesignation providing an indication whether the human subject has or isat risk of CAN/IFTA.
 3. The method of claim 2, wherein the expressionlevel of each of the at least genes ANTXR2, SYNPO, VSIG4, GFI1B, SPTLC2,RNF175, and EST56 is assigned a value on a normalized scale of valuesassociated with a range of expression levels in kidney transplantpatients with and without CAN/IFTA.
 4. The method of claim 2, whereinthe expression level of each of the at least genes ANTXR2, SYNPO, VSIG4,GFI1B, SPTLC2, RNF175, and BST56 is assigned a value or otherdesignation providing an indication that the human subject has or is atrisk of CAN/IFTA, lacks and is not at risk of CAN/IFTA, or that theexpression level is uninformative.
 5. The method of claim 2, wherein (c)further comprises combining the values or designations for each of thegenes to provide a combined value or designation providing an indicationwhether the human subject has or is at risk of CAN/IFTA.
 6. The methodof claim 5, wherein the method is repeated at different times on thehuman subject.
 7. The method of claim 5, wherein a change in thecombined value or designation over time provides an indication of theeffectiveness of the immunosuppressant drug received by the humansubject.
 8. The method of claim 1, wherein the human subject hasundergone a kidney transplant within 1-10 years of performing step (a).9. The method of claim 1, wherein the blood sample is a peripheral bloodsample.
 10. The method of claim 9, wherein the peripheral blood sampleis a peripheral blood lymphocyte sample.
 11. The method of claim 1,wherein the blood sample is a blood plasma sample.
 12. The method ofclaim 1, wherein the target nucleic acids are mRNA extracted from theblood sample from the human subject.
 13. The method of claim 12, whereinthe target nucleic acids are nucleic acids derived from the mRNAextracted from the blood sample from the human subject.
 14. The methodof claim 13, wherein the target nucleic acids are DNA derived from themRNA extracted from the blood sample from the human subject.
 15. Themethod of claim 13, wherein the detecting the expression levels in thehuman subject comprises one or more of the following: (a) hybridizingthe mRNA to an array; (b) nucleic acid amplification; (c) monitoring theformation of an amplification product; or (d) synthesizing a nucleicacid using the mRNA as a template.
 16. The method of claim 1, whereinthe prognosing, diagnosing or monitoring CAN/IFTA in the transplantedkidney of the human subject in step (d) further comprises performing anadditional procedure to detect CAN/IFTA or risk thereof if the detectingexpression levels provides an indication the subject has or is at riskof CAN/IFTA.
 17. The method of claim 16, wherein the additionalprocedure is a kidney biopsy.
 18. The method of claim 1, furthercomprising determining baseline values of expression levels in the humansubject before a kidney transplant.
 19. The method of claim 18, whereinprognosing, diagnosing or monitoring CAN/IFTA in the human subjectcomprises comparing the baseline values of expression levels in thehuman subject before the kidney transplant with the expression levels inthe human subject after the kidney transplant.
 20. The method of claim16, wherein the additional procedure is a creatinine or glomerularfiltration rate analysis.
 21. The method of claim 12, wherein thedetecting the expression levels in the human subject compriseshybridizing the mRNA to an array.
 22. The method of claim 14, whereinthe detecting the expression levels in the human subject compriseshybridizing the DNA to an array.
 23. The method of claim 1, wherein themethod comprises diagnosing CAN/IFTA in the human subject from theexpression levels detected in step (c).
 24. The method of claim 1,wherein the method comprises prognosing, diagnosing or monitoringCAN/IFTA in the transplanted kidney of the human subject when theexpression levels of at least 50 genes exhibit a statisticallysignificant fold change.
 25. The method of claim 1, wherein the methodcomprises prognosing, diagnosing or monitoring CAN/IFTA in thetransplanted kidney of the human subject when the expression levels ofat least 100 genes exhibit a statistically significant fold change. 26.The method of claim 1, wherein the transplanted kidney is a transplantedkidney organ.
 27. The method of claim 1, wherein the transplanted kidneyis transplanted kidney tissues or cells.
 28. The method of claim 1,wherein the method comprises administering an increased dose of theimmunosuppressant drug to the human subject in order to treat or preventthe CAN/IFTA prognosed, diagnosed or monitored in the transplantedkidney of the human subject in step (d).
 29. The method of claim 1,wherein the method comprises administering a new immunosuppressant drugto the human subject in order to treat or prevent the CAN/IFTAprognosed, diagnosed or monitored in the transplanted kidney of thehuman subject in step (d).
 30. The method of claim 1, wherein theimmunosuppressant drug or the new immunosuppressant drug is acalcineurin inhibitor.
 31. The method of claim 30, wherein thecalcineurin inhibitor is cyclosporin or tacrolimus.
 32. The method ofclaim 1, wherein the immunosuppressant drug or the new immunosuppressantdrug is an mTOR inhibitor.
 33. The method of claim 32, wherein the mTORinhibitor is sirolimus or everolimus.
 34. The method of claim 1, whereinthe immunosuppressant drug or new immunosuppressant drug is selectedfrom the group consisting of: azathioprine, mycophenolic acid,prednisolone, hydrocortisone, basiliximab, daclizumab, orthoclone,anti-thymocyte globulin, anti-lymphocyte globulin, an anti-proliferativedrug, and an anti-T cell antibody.
 35. The method of claim 1, whereinthe method comprises prognosing, diagnosing or monitoring CAN/IFTA inthe transplanted kidney of the human subject when the expression levelsof at least 20 genes from Table A, B, C, D, E, F, G, H, I and/or J andless than 1000 total genes exhibit a statistically significant foldchange.
 36. The method of claim 1, wherein the method comprisesprognosing, diagnosing or monitoring CAN/IFTA in the transplanted kidneyof the human subject when the expression levels of at least 40 and up to500 genes exhibit a statistically significant fold change.
 37. Themethod of claim 1, wherein step (d) of the method comprises diagnosingCAN/IFTA in the transplanted kidney of the human subject.
 38. The methodof claim 36, wherein step (e) comprises administering the increased doseof the immunosuppressant drug to the human subject in order to treat theCAN/IFTA diagnosed in the transplanted kidney of the human subject instep (d).
 39. The method of claim 36, wherein step (e) comprisesadministering the new immunosuppressant drug to the human subject inorder to treat the CAN/IFTA diagnosed in the transplanted kidney of thehuman subject in step (d).